beta-carotene and Adenocarcinoma

Lung cancer is the major cause of death in industrialized western societies. Its link to tobacco abuse is well established and efforts should be made to eliminate this potent environmental carcinogen. The concept of chemoprevention, the use of agents to inhibit and reverse lung cancer carcinogenesis, has great appeal. The CARET study, conducted in 18,000 high-risk smokers in the US, found that a combination of beta-carotene and retinyl palmitate resulted in a 28% increase in the incidence of lung cancer. A similar study conducted in Finland, the ATBC trial utilizing alpha tocopherol and beta-carotene, had similar findings for the group taking beta-carotene. These two trials have caused a rethinking of the use of natural compounds as chemoprevention agents. These agents should no longer be regarded as harmless, but as having potential toxicities. A new approach in the chemoprevention of cancer has been the concept of surrogate endpoints, biological changes that are on the pathway to cancer. Trials are underway to determine what are appropriate surrogate endpoints for lung cancer chemoprevention trials.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Anticarcinogenic Agents; beta Carotene; Carotenoids; Chromosomes, Human, Pair 3; Clinical Trials as Topic; Cocarcinogenesis; Cytochrome P-450 CYP1A1; Diterpenes; Female; Flavonoids; Genetic Predisposition to Disease; Glutathione Transferase; Humans; Inactivation, Metabolic; Incidence; Lung Neoplasms; Lycopene; Male; Middle Aged; Polymorphism, Genetic; Precancerous Conditions; Retinoids; Retinyl Esters; Risk Factors; Selenium; Smoking; Smoking Prevention; Trace Elements; Treatment Outcome; Vitamin A; Vitamin E

Many epidemiologic studies have examined the association between C-reactive protein (CRP) and risk of cancer with inconsistent results.. We conducted two nested, case-control studies in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) and Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) to test whether prediagnostic circulating CRP concentrations were associated with pancreatic adenocarcinoma. Between 1985 and 2004, 311 cases occurred in ATBC and between 1994 and 2006, 182 cases occurred in PLCO. Controls (n = 510 in ATBC, n = 374 in PLCO) were alive at the time the case was diagnosed and were matched by age, date of blood draw, sex, and race. We used conditional logistic regression adjusted for smoking to calculate OR and 95% CI for pancreatic cancer.. CRP concentrations (ng/mL) tended to be inversely or not associated with pancreatic cancer risk in ATBC, PLCO, and combined analyses [per standardized quintile increase in CRP, continuous OR = 0.94 (95% CI, 0.89-0.99), OR = 0.99 (95% CI, 0.95-1.04), OR = 0.98 (95% CI, 0.95-1.01), respectively]. In combined analyses, we observed a significant interaction (P(interaction) = 0.02) such that inverse associations were suggestive in younger (OR = 0.95; 95% CI, 0.90-1.01), but not older, participants.. Our results do not support the hypothesis that higher CRP concentrations are associated with incident pancreatic cancer.. Our results highlight the importance of investigating more specific biomarkers for inflammation that may reflect the biological mechanisms underlying pancreatic cancer in prospective cohort studies.

Topics: Adenocarcinoma; Aged; alpha-Tocopherol; beta Carotene; C-Reactive Protein; Case-Control Studies; Cohort Studies; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pancreatic Neoplasms; Placebos; Prognosis; Risk Assessment; Risk Factors; Vitamins

The nuclear hormone receptor peroxisome proliferator-activated receptor-gamma (PPAR-gamma) may play a role in prostate carcinogenesis. We examined the association between the PPAR-gamma Pro12Ala polymorphism and prostate cancer risk in a cohort of Finnish male smokers. In a nested case-control analysis that included 193 prostate cancer cases and 188 matched controls, we found no significant association between this polymorphism and prostate cancer risk (odds ratio, OR=1.27, 95% confidence interval, CI: 0.83-1.94), or significant trend or association with tumor stage (OR=1.28, 95% CI: 0.54-3.04 for metastatic disease) or grade (OR=1.57, 95% CI: 0.63-3.91 for poorly differentiated disease). The Pro12Ala polymorphism does not appear to play a significant role in prostate cancer risk in this cohort of men.

Topics: Adenocarcinoma; Aged; alpha-Tocopherol; Amino Acid Substitution; Anticarcinogenic Agents; beta Carotene; Case-Control Studies; Cell Differentiation; Cohort Studies; DNA Mutational Analysis; Finland; Genetic Predisposition to Disease; Genotype; Humans; Incidence; Male; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Prostatic Neoplasms; Receptors, Cytoplasmic and Nuclear; Risk; Smoking; Transcription Factors

Higher blood levels of alpha-tocopherol, the predominant form of vitamin E, have been associated in some studies with a reduced risk of lung cancer, but other studies have yielded conflicting results. To clarify this association, we examined the relationship between prospectively collected serum alpha-tocopherol and lung cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort.. The ATBC Study was a randomized, clinical trial of 29 133 white male smokers from Finland who were 50-69 years old and who had received alpha-tocopherol (50 mg), beta-carotene (20 mg), both, or neither daily for 5-8 years. Data regarding medical histories, smoking, and dietary factors were obtained at study entry, as was a serum specimen for baseline alpha-tocopherol determination. alpha-Tocopherol measurements were available for 29 102 of the men, among whom 1144 incident cases of lung cancer were diagnosed during a median observation period of 7.7 years. The association between alpha-tocopherol and lung cancer was evaluated with the use of multivariate proportional hazards regression.. A 19% reduction in lung cancer incidence was observed in the highest versus lowest quintile of serum alpha-tocopherol (relative risk = 0.81; 95% confidence interval = 0. 67-0.97). There was a stronger inverse association among younger men (<60 years), among men with less cumulative tobacco exposure (<40 years of smoking), and possibly among men receiving alpha-tocopherol supplementation.. In the ATBC Study cohort, higher serum alpha-tocopherol status is associated with lower lung cancer risk; this relationship appears stronger among younger persons and among those with less cumulative smoke exposure. These findings suggest that high levels of alpha-tocopherol, if present during the early critical stages of tumorigenesis, may inhibit lung cancer development.

Topics: Adenocarcinoma; Aged; beta Carotene; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Dietary Supplements; Finland; Humans; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Risk; Risk Factors; Smoking; Treatment Outcome; Vitamin E

A randomized nutrition intervention trial was conducted among 29,584 adult residents of Linxian, China, to examine the effects of vitamin/mineral supplementation on the occurrence of esophageal/gastric cardia cancer in this high-risk population. A fractional factorial study design allowed evaluations of four different combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta-carotene, vitamin E, and selenium. During the 5.25-year intervention, significant reductions in total mortality, total cancer mortality, and stomach cancer mortality occurred among those receiving beta-carotene, vitamin E, and selenium. At the end of intervention, an endoscopic survey was carried out in a sample of subjects to see if the nutritional supplements had affected the prevalence of clinically silent precancerous lesions and early invasive cancers of the esophagus or stomach. Endoscopy was performed on 391 individuals from two study villages. The prevalences of esophageal and gastric dysplasia and cancer were compared by nutrient factor. Cancer or dysplasia was diagnosed in 15% of the participants. No statistically significant reductions in the prevalence of esophageal or gastric dysplasia or cancer were seen for any of the four vitamin/mineral combinations. The greatest reduction in risk (odds ratio, 0.38; P = 0.09) was seen for the effect of retinol and zinc on the prevalence of gastric cancer. Although no significant protective effects were seen in this endoscopic survey, there was a suggestion that supplementation with retinol and zinc may protect against the development of gastric neoplasia in this high-risk population. Additional studies with larger numbers of endpoints will be needed to further evaluate this possibility.

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; beta Carotene; Carotenoids; Cell Transformation, Neoplastic; China; Cross-Cultural Comparison; Cross-Sectional Studies; Double-Blind Method; Endoscopy, Gastrointestinal; Esophageal Neoplasms; Esophagus; Female; Gastric Mucosa; Humans; Incidence; Male; Middle Aged; Minerals; Molybdenum; Niacin; Precancerous Conditions; Riboflavin; Rural Population; Selenium; Stomach Neoplasms; Survival Rate; Vitamin A; Vitamin E; Vitamins; Zinc

Linxian, China has some of the highest rates of esophageal/gastric cardia cancer in the world, and epidemiological evidence suggests that chronically low intake of micronutrients may contribute to these high cancer rates. To examine whether supplementation with multiple vitamins and minerals can affect the occurrence of esophageal/gastric cardia cancer in this population, a two-arm randomized nutrition intervention trial was conducted among 3318 Linxian residents with cytological evidence of esophageal dysplasia. During the 6-year intervention, esophageal/gastric cardia cancer mortality was 8% lower among those receiving the active supplements. After 30 and 72 months of intervention, endoscopic surveys were carried out to see if the nutritional supplements had affected the prevalence of clinically silent precancerous lesions and early invasive cancers of the esophagus and stomach. In the first survey, in 1987, 833 subjects were endoscoped; in the second survey, in 1991, 396 subjects were examined. The histological diagnoses from each survey were compared by treatment group. Cancer or dysplasia was diagnosed in 28% of the subjects endoscoped in 1987 and 24% of those examined in 1991. The odds ratio for subjects in the treatment group (versus those in the placebo group) having esophageal or gastric dysplasia or cancer was 0.84 (95% confidence interval, 0.61-1.15) in 1987 and 0.86 (0.54-1.38) in 1991. Although modest protective effects on worst overall diagnosis were seen in the supplemented group in both surveys, none of the results was statistically significant, and the findings must be considered inconclusive.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Adult; Aged; Ascorbic Acid; beta Carotene; Carotenoids; Cell Transformation, Neoplastic; Cross-Cultural Comparison; Double-Blind Method; Endoscopy, Gastrointestinal; Esophageal Neoplasms; Esophagus; Female; Follow-Up Studies; Gastric Mucosa; Humans; Male; Middle Aged; Minerals; Molybdenum; Niacin; Precancerous Conditions; Riboflavin; Rural Population; Selenium; Stomach Neoplasms; Survival Rate; Vitamin A; Vitamin E; Vitamins; Zinc

Topics: Adenocarcinoma; alpha-Tocopherol; Antioxidants; beta Carotene; Caco-2 Cells; Carbon Dioxide; Chemical Fractionation; Cytotoxins; Fatty Acids; Flavonoids; Fruit; Humans; Lycium; Phenols; Plant Oils; Triglycerides

Despite decades of concerted epidemiological research, relatively little is known about the etiology of prostate cancer. As genome-wide association studies have identified numerous genetic variants, so metabolomic profiling of blood and other tissues represents an agnostic, "broad-spectrum" approach for examining potential metabolic biomarkers of prostate cancer risk. To this end, we conducted a prospective analysis of prostate cancer within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort based on 200 cases (100 aggressive) and 200 controls (age- and blood collection date-matched) with fasting serum collected up to 20 years prior to case diagnoses. Ultrahigh performance liquid chromatography/mass spectroscopy and gas chromatography/mass spectroscopy identified 626 compounds detected in >95% of the men and the odds ratio per 1-standard deviation increase in log-metabolite levels and risk were estimated using conditional logistic regression. We observed strong inverse associations between energy and lipid metabolites and aggressive cancer (p = 0.018 and p = 0.041, respectively, for chemical class over-representation). Inositol-1-phosphate showed the strongest association (OR = 0.56, 95% CI = 0.39-0.81, p = 0.002) and glycerophospholipids and fatty acids were heavily represented; e.g., oleoyl-linoleoyl-glycerophosphoinositol (OR = 0.64, p = 0.004), 1-stearoylglycerophosphoglycerol (OR=0.65, p = 0.025), stearate (OR=0.65, p = 0.010) and docosadienoate (OR = 0.66, p = 0.014). Both alpha-ketoglutarate and citrate were associated with aggressive disease risk (OR = 0.69, 95% CI = 0.51-0.94, p = 0.02; OR = 0.69, 95% CI = 0.50-0.95, p = 0.02), as were elevated thyroxine and trimethylamine oxide (OR = 1.65, 95% CI = 1.08-2.54, p = 0.021; and OR = 1.36, 95% CI = 1.02-1.81, p = 0.039). Serum PSA adjustment did not alter the findings. Our data reveal several metabolomic leads that may have pathophysiological relevance to prostate carcinogenesis and should be examined through additional research.

Topics: Adenocarcinoma; alpha-Tocopherol; beta Carotene; Biomarkers, Tumor; Humans; Male; Metabolome; Metabolomics; Middle Aged; Prospective Studies; Prostatic Neoplasms

Lycopene and beta-carotene are carotenoids widely distributed in fruits and vegetables, with potential anticancer activity. Epidemiological trials rarely provide evidence for the mechanisms of action of these compounds, and their biological effects at different times of treatment are still unclear. The aim of the present study was to determine the effect of carotenoids on the cell cycle and cell viability in human breast cancer cell lines. Human breast cell lines were treated with carotenoids (0.5-10 μM) for 48 and 96 h. Cell viability was monitored using the MTT method (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; thiazolyl blue). The cell cycle was analyzed by flow cytometry, and apoptotic cells were identified by annexin/propidium iodide (PI) biomarkers. Our data showed a significant decrease in the number of viable breast cancer cells on treatment with carotenoids. Carotenoids also promoted cell-cycle arrest followed by decreased cell viability in the majority of cell lines after 96 h, compared to controls. Furthermore, an increase in apoptosis was observed in cell lines when cells were treated with carotenoids. Our findings show the capacity of lycopene and beta-carotene to inhibit cell proliferation, arrest the cell cycle in different phases, and increase apoptosis. These findings indicate that the effect was cell type-dependent and that carotenoids are potential agents for biological interference with cancer.

Topics: Adenocarcinoma; Anticarcinogenic Agents; Apoptosis; beta Carotene; Blotting, Western; Breast Neoplasms; Carotenoids; Cell Cycle Checkpoints; Cell Proliferation; Female; Flow Cytometry; Humans; Lycopene; Tumor Cells, Cultured; Vitamins

While dietary antioxidants are emerging as potentially modifiable risk factors for esophageal adenocarcinoma (EAC), studies on dietary antioxidants and its precursor Barrett's esophagus (BE) are limited. The present study extends previous work on BE by investigating risks of nondysplastic BE, dysplastic BE and EAC associated with intake of antioxidants such as vitamin C, vitamin E, β-carotene, and selenium. Age and sex matched control subjects (n=577 for BE; n=1,507 for EAC) were sampled from an Australian population register. Information on demography, and well established EAC risk factors were obtained using self-administered questionnaires. Intake of antioxidants for patients newly diagnosed with nondysplastic BE (n=266), dysplastic BE (n=101), or EAC (n=299), aged 18-79 years, were obtained using a food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable adjusted logistic regression models. High intake of β-carotene from food and supplement sources combined was inversely associated with risk of dysplastic BE (OR Q4 vs. Q1=0.45; 95%CI: 0.20-1.00). High intake of vitamin E from food sources (OR Q4 vs. Q1=0.43; 95%CI: 0.28-0.67), from food and supplements combined (OR Q4 vs. Q1=0.64; 95%CI: 0.43-0.96), and a high antioxidant index score were inversely associated with risk of EAC. We found no significant trends between intake of β-carotene, vitamin C, vitamin E, and selenium and risk of nondysplastic or dysplastic BE. However, our data suggest that a high intake of β-carotene may be associated with decreased risk of dysplastic BE.

Topics: Adenocarcinoma; Adult; Aged; Antioxidants; Ascorbic Acid; Australia; Barrett Esophagus; beta Carotene; Energy Intake; Esophageal Neoplasms; Feeding Behavior; Female; Fruit; Humans; Male; Middle Aged; Risk Factors; Selenium; Vegetables; Vitamin E

Studying gene-environment interactions may provide insight about mechanisms underpinning the reported association between chromosome 15q24-25.1 variation and lung cancer susceptibility.. In a nested case-control study comparing 746 lung cancer cases to 1,477 controls, all of whom were non-Hispanic white smokers in the β-Carotene and Retinol Efficacy Trial, we examined whether lung cancer risk is associated with single nucleotide polymorphisms (SNPs) tagging the AGPHD1, CHRNA5, CHRNA3, and CHRNB4 genes and whether such risk is modified by diet and other characteristics. Intake of fruits and vegetables, their botanical groups, and specific nutrients were ascertained generally at baseline by food-frequency questionnaire.. Several sets of SNPs in high linkage disequilibrium were found: one set associated with a 27-34% increase and two sets associated with a 13-19% decrease in risk per minor allele. Associations were most prominent for the set including the non-synonymous SNP rs16969968. The rs16969968-lung cancer association did not differ by intake level of most dietary factors examined, but was stronger for individuals diagnosed at < 70 years of age or having a baseline smoking history of <40 cigarette pack-years.. Our data suggests that diet has little influence on the relation between chromosome 15q24-25.1 variation and lung cancer risk.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Aged; Alleles; beta Carotene; Case-Control Studies; Diet; Female; Genetic Predisposition to Disease; Humans; Lung Neoplasms; Male; Middle Aged; Polymorphism, Single Nucleotide; Risk; Smoking

The decoction of the whole plant of Elephantopus mollis Kunth. is traditionally consumed to treat various free radical-mediated diseases including cancer and diabetes.. This study was initiated to determine whether the most effective antioxidant compound isolated from the whole plant of Elephantopus mollis can also contribute to its claimed traditional values as anticancer and antidiabetes agents.. An active antiradical phenolic compound (3,4-di-O-caffeoyl quinic acid) was isolated from the methanol extract (with the highest in polyphenolic content) and their antioxidant activities were compared using four different assays, that are DPPH, FRAP, metal chelating, and β-carotene bleaching tests. The compound was also evaluated for its cytotoxic activity, apoptotic induction and anti-glucosidase efficacies using methylene blue, DeadEnd™ assay and α-glucosidase assays, respectively.. The compound acted as a greater primary antioxidant than its methanol extract, by having higher ferric reducing activity (EC(50) 2.18±0.05 μg/ml), β-carotene bleaching activity (EC(50) 23.85±0.65 μg/ml) and DPPH scavenging activity (EC(50) 68.91±5.44μg/ml), whereas the methanol extract exhibited higher secondary antioxidant activity as a metal chelator with lower EC(50) value (49.39±3.68 μg/ml) than the compound. Cytotoxicity screening of this compound exhibited a remarkable dose-dependent inhibitory effect on NCI-H23 (human lung adenocarcinoma) cell lines (EC(50) 3.26±0.35 μg/ml) and was found to be apoptotic in nature based on a clear indication of DNA fragmentation. This compound also displayed a concentration-dependent α-glucosidase inhibition with EC(50) 241.80±14.29 μg/ml.. The findings indicate the major role of 3,4-di-O-caffeoyl quinic acid to antioxidant capacities of Elephantopus mollis extracts. The compound also exerted apoptosis-mediated cytotoxicity and α-glucosidase inhibitory effects and is thus a promising non toxic agent in treating cancer and type 2 diabetes mellitus.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Antioxidants; Apoptosis; Asteraceae; beta Carotene; Biphenyl Compounds; Cell Line, Tumor; Chelating Agents; Chlorogenic Acid; DNA Fragmentation; Dose-Response Relationship, Drug; Enzyme Inhibitors; Ferric Compounds; Glycoside Hydrolase Inhibitors; Humans; Lung Neoplasms; Picrates; Plant Extracts; Polyphenols

Diabetes, obesity, and cigarette smoke, consistent risk factors for pancreatic cancer, are sources of oxidative stress in humans that could cause mitochondrial DNA (mtDNA) damage and increase mtDNA copy number. To test whether higher mtDNA copy number is associated with increased incident pancreatic cancer, we conducted a nested case-control study in the Alpha-Tocopherol Beta Carotene Cancer Prevention (ATBC) Study cohort of male smokers, aged 50 to 69 years at baseline. Between 1992 and 2004, 203 incident cases of pancreatic adenocarcinoma occurred (follow-up: 12 years) among participants, with whole blood samples used for mtDNA extraction. For these cases and 656 controls, we calculated ORs and 95% CIs using unconditional logistic regression, adjusting for age, smoking, and diabetes history. All statistical tests were two sided. Higher mtDNA copy number was significantly associated with increased pancreatic cancer risk (highest vs. lowest mtDNA copy number quintile, OR = 1.64, 95% CI = 1.01-2.67, continuous OR = 1.14, 95% CI 1.06-1.23), particularly for cases diagnosed during the first 7 years of follow-up (OR = 2.14, 95% CI = 1.16-3.96, P(trend) = 0.01, continuous OR = 1.21, 95% CI = 1.10-1.33), but not for cases occurring during follow-up of 7 years or greater (OR = 1.14, 95% CI = 0.53-2.45, continuous OR = 1.05, 95% CI = 0.93-1.18). Our results support the hypothesis that mtDNA copy number is associated with pancreatic cancer and could possibly serve as a biomarker for pancreatic cancer development.

Topics: Adenocarcinoma; alpha-Tocopherol; beta Carotene; Biomarkers, Tumor; Case-Control Studies; Diabetes Complications; DNA; DNA Copy Number Variations; DNA, Mitochondrial; Double-Blind Method; Humans; Male; Middle Aged; Obesity; Pancreatic Neoplasms; Polymerase Chain Reaction; Prognosis; Risk Factors; Smoking

Lycopene beta-cyclase (tlcy-b) tomatoes, obtained by modulating carotenogenesis via genetic engineering, contain a large amount of beta-carotene, as clearly visible by their intense orange colour. In the present study we have subjected tlcy-b tomatoes to an in vitro simulated digestion and analysed the effects of digestate on cell proliferation. To this aim we used HT-29 human colon adenocarcinoma cells, grown in monolayers, as a model. Digested tomatoes were diluted (20 ml, 50 ml and 100 ml/l) in culture medium and added to the cells for different incubation times (24 h, 48 h and 72 h). Inhibition of cell growth by tomato digestate was dose-dependent and resulted from an arrest of cell cycle progression at the G0/G1 and G2/M phase and by apoptosis induction. A down-regulation of cyclin D1, Bcl-2 and Bcl-xl expression was observed. We also found that heat treatment of samples before digestion enhanced beta-carotene release and therefore cell growth inhibition. To induce with purified beta-carotene solubilised in tetrahydrofuran the same cell growth inhibition obtained with the tomato digestate, a higher amount of the carotenoid was necessary, suggesting that beta-carotene micellarised during digestion is utilised more efficiently by the cells, but also that other tomato molecules, reasonably made available during digestion, may be present and cooperate with beta-carotene in promoting cell growth arrest.

Topics: Adenocarcinoma; Analysis of Variance; Animals; Apoptosis; bcl-X Protein; beta Carotene; Biomarkers; Caspase 3; Colonic Neoplasms; Cyclin D1; Digestion; Down-Regulation; Genes, bcl-2; Genetic Markers; HT29 Cells; Humans; Interphase; Intramolecular Lyases; Plants, Genetically Modified; Solanum lycopersicum; Swine

beta-Carotene has shown cancer-preventive effects in preclinical studies while increasing lung cancer mortality in clinical trials. We have shown that beta-carotene stimulates cAMP signalling in vitro. Here, we have tested the hypothesis that beta-carotene promotes the development of pulmonary adenocarcinoma (PAC) in vivo via cAMP signalling.. PAC was induced in hamsters with the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), followed by beta-carotene for 1.5 years. Incidence, multiplicity and size of lung tumours were recorded, and phosphorylated CREB and ERK1/2 in tumour cells were determined by Western blots. Cyclic AMP in blood cells was analysed by immunoassays, retinoids in serum and lungs by HPLC.. beta-Carotene increased lung tumour multiplicity, lung tumour size, blood cell cAMP, serum and lung levels of retinoids and induced p-CREB and p-ERK1/2 in lung tumours.. Our data suggest that beta-carotene promotes the development of PAC via increased cAMP signalling.

Topics: Adenocarcinoma; Animals; beta Carotene; Biological Assay; Blotting, Western; Cricetinae; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Extracellular Signal-Regulated MAP Kinases; Lung Neoplasms; Male; Mesocricetus; Models, Animal; Nitrosamines; Phosphorylation; Random Allocation; Retinoids; Signal Transduction; Time Factors

Differential diagnosis for epithelial tissues of normal human gastric, undifferentiation gastric adenocarcinoma, gastric squamous cell carcinomas, and poorly differentiated gastric adenocarcinoma were studied using the Kubelka-Munk spectral function of the DNA and protein absorption bands at 260 and 280 nm in vitro. Diffuse reflectance spectra of tissue were measured using a spectrophotometer with an integrating sphere attachment. The results of measurement showed that for the spectral range from 250 to 650 nm, pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the DNA absorption bands at 260 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 68.5% (p < 0.05), 146.5% (p < 0.05), 282.4% (p < 0.05), 32.4% (p < 0.05), 56.00 (p < 0.05) and 83.0% (p < 0.05) respectively. And pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the protein absorption bands at 280 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 86.8% (p < 0.05), 262.9% (p < 0.05), 660.1% (p < 0.05) and 34% (p < 0.05), 72. 2% (p < 0.05), 113.5% (p < 0.05) respectively. And pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the carotene absorption bands at 480 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 59.5% (p < 0

Topics: Adenocarcinoma; beta Carotene; Carcinoma, Squamous Cell; DNA; Gastric Mucosa; Humans; Proteins; Spectrophotometry; Stomach Neoplasms

The aim of this study was to evaluate the inhibitory growth effects of different potential chemopreventive agents in vitro and to determine their influence on PSA mRNA and protein expression with an established screening platform.. LNCaP and C4-2 cells were incubated with genistein, seleno-L-methionine, lycopene, DL-alpha-tocopherol, and trans-beta-carotene at three different concentrations and cell growth was determined by the MTT assay. PSA mRNA expression was assessed by quantitative real-time RT-PCR and secreted PSA protein levels were quantified by the microparticle enzyme immunoassay.. Genistein, seleno-l-methionine and lycopene inhibited LNCaP cell growth, and the proliferation of C4-2 cells was suppressed by seleno-L-methionine and lycopene. PSA mRNA expression was downregulated by genistein in LNCaP but not C4-2 cells. No other compound tested altered PSA mRNA expression. PSA protein expression was downregulated by genistein, seleno-L-methionine, DL-alpha-tocopherol in LNCaP cells. In C4-2 cells only genistein significantly reduced the secretion of PSA protein.. In the LNCaP progression model PSA expression depends on the compound, its concentration and on the hormonal dependence of the cell line used and does not necessarily reflect cell growth or death. Before potential substances are evaluated in clinical trials using PSA as a surrogate end point marker, their effect on PSA mRNA and protein expression has to be considered to correctly assess treatment response by PSA.

Topics: Adenocarcinoma; alpha-Tocopherol; Anticarcinogenic Agents; beta Carotene; Biomarkers, Tumor; Carotenoids; Cell Line, Tumor; Cell Proliferation; Disease Progression; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Genistein; Humans; Lycopene; Male; Prostate-Specific Antigen; Prostatic Neoplasms; RNA, Messenger; Selenomethionine; Vitamins

An alpha-tocopherol, beta-carotene supplementation trial (ATBC) and a chemoprevention trial with beta-carotene and retinoids (CARET trial) were conducted in the 1990s in populations at risk for the development of lung cancer. Both trials had to be discontinued due to significant increases in lung cancer and cardiovascular mortality. Clinical trials to test the cancer preventive effects of beta-carotene are still ongoing, and high concentrations of this provitamin are contained in numerous dietary supplements. Using a cell line derived from a human pulmonary adenocarcinoma (PAC) of Clara cell lineage and immortalized human small airway epithelial cells, our data show that low concentrations of beta-carotene that can be realistically expected in human tissues after oral administration caused a significant increase in intracellular cAMP and activated PKA, as well as in phosphorylation of ERK1/2 and CREB. Furthermore, the proliferation of cells was significantly stimulated by identical concentrations of beta-carotene as monitored by MTT assays. Control experiments with retinol also showed stimulation of cell proliferation and activation of PKA in both cell lines. In light of the fact that PAC is the leading type of lung cancer, these findings suggest that the growth promoting effects of beta-carotene on this cancer type observed in our experiments may have contributed to the unfortunate outcome of the ATBC and CARET trials. This interpretation is supported by the fact that elevated levels of cAMP in the cardiovascular system play a major role in the genesis of cardiovascular disease, which was also greatly promoted in the CARET trial. Our data challenge the widely accepted view that beta-carotene may be useful as a cancer preventive agent.

Topics: Adenocarcinoma; Analysis of Variance; beta Carotene; Blotting, Western; Cell Line; Cell Line, Tumor; Cell Proliferation; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Cyclic AMP-Dependent Protein Kinases; Dose-Response Relationship, Drug; Enzyme Activation; Epithelial Cells; Humans; Lung; Lung Neoplasms; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Phosphorylation; Protein Serine-Threonine Kinases; Time Factors; Vitamins

Colonization with Helicobacter pylori is a risk factor for gastric adenocarcinoma, but the magnitude of this association and its relationship to anatomic location of the cancer, duration of follow-up, age at diagnosis, histologic subtype, and H. pylori strain differences are less clear. We conducted a prospective nested case-control study of H. pylori serology to address these questions.. Case and control subjects were selected from the 29,133 50- to 69-year-old males recruited into the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. At baseline, detailed demographic data and a serum sample were collected. From 1985 to 1999, 243 incident cases of gastric adenocarcinoma were diagnosed in cohort members. Serum samples from 234 case subjects (173 with noncardia gastric cancers and 61 with gastric cardia cancers) and 234 age-matched control subjects were assayed for antibodies against H. pylori whole-cell and CagA antigens. We fit conditional logistic regression models to estimate the unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association of H. pylori seropositivity, defined as seropositivity to either whole-cell or CagA antigens, with noncardia gastric and gastric cardia cancers. All statistical tests were two-sided.. H. pylori seropositivity was strongly associated with the risk of noncardia gastric cancer (adjusted OR = 7.9, 95% CI = 3.0 to 20.9) but was inversely associated with the risk of gastric cardia cancer (adjusted OR = 0.31, 95% CI = 0.11 to 0.89). H. pylori seropositivity rates did not vary statistically significantly by length of follow-up, age at diagnosis, or histologic subtype. A calculation of rates showed that the absolute risks of noncardia gastric and cardia gastric adenocarcinomas in the H. pylori-positive participants of this cohort would be 63 and 12 per 100,000 person-years, respectively, whereas corresponding rates in H. pylori-negative participants would be 8 and 37 per 100,000 person-years, respectively.. H. pylori is a strong risk factor for noncardia gastric cancer but is inversely associated with the risk of gastric cardia cancer. These findings bolster the hypothesis that decreasing H. pylori prevalence during the past century may have contributed to lower rates of noncardia cancer and higher rates of cardia cancer in Western countries.

Topics: Adenocarcinoma; Aged; alpha-Tocopherol; Antigens, Bacterial; Antioxidants; Bacterial Proteins; beta Carotene; Cardia; Case-Control Studies; Developed Countries; Dietary Supplements; Finland; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Neoplasms; Odds Ratio; Prevalence; Primary Prevention; Prospective Studies; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Seroepidemiologic Studies; Stomach Neoplasms; Time Factors

We demonstrated previously that beta-carotene may affect cell growth by a redox mechanism. The purpose of this study was to determine whether the redox-sensitive transcription factor nuclear factor (NF)-kappaB may be involved in the growth-inhibitory and proapoptotic effects of the carotenoid. To test this hypothesis, human leukemic cells (HL-60) and colon adenocarcinoma cells (LS-174 and WiDr) were treated with beta-carotene, alone or in combination with alpha-tocopherol or N-acetylcysteine, and changes in 1) cell oxidative status, 2) cell growth and apoptosis, 3) DNA-binding activity of NF-kappaB and 4) expression of c-myc, a NF-kappaB target gene involved in apoptosis, were evaluated. In HL-60 cells, beta-carotene induced a significant increase in reactive oxygen species (ROS) production (P < 0.001) and in oxidized glutathione (GSSG) content (P < 0.005) at concentrations >/=10 micro mol/L. These effects were always accompanied by a sustained elevation of NF-kappaB and by a significant inhibition (P < 0.002) of cell growth. NF-kappaB DNA-binding activity increased at 3 h and persisted for at least 48 h. Colon adenocarcinoma cells displayed substantial differences in their sensitivity to beta-carotene, exhibiting increased ROS levels and activation of NF-kappaB at concentrations much lower in LS-174 cells (2.5-5.0 micro mol/L) than in WiDr cells (50-100 micro mol/L). In all cell lines studied, alpha-tocopherol and N-acetylcysteine inhibited the effects of beta-carotene on NF-kappaB, cell growth and apoptosis, and normalized the increased expression of c-myc induced by the carotenoid. These data suggest that the redox regulation of NF-kappaB induced by beta-carotene is involved in the growth-inhibitory and proapoptotic effects of the carotenoid in tumor cells.

Topics: Acetylcysteine; Adenocarcinoma; Apoptosis; beta Carotene; Colonic Neoplasms; Genes, myc; HL-60 Cells; Humans; NF-kappa B; Oxidation-Reduction; Reactive Oxygen Species

In addition to its antioxidant activity, beta-carotene (BC) is known to enhance gap junction intercellular communication (GJIC) by up-regulation of connexin 43 (Cx43), an action that may be important in its control of tumor growth. Surprisingly, two clinical trials on supplemental BC suggest that BC may increase lung cancer incidence in smokers. Recently, an animal study indicated that a very high dose of BC (50 mg/kg b.w./day for 5 days) decreases GJIC in rat liver, while a lower dose (5 mg/kg b.w./day) increases GJIC. It is unclear how high-doses of BC inhibit GJIC. In this study, we tested whether oxidized BC (OBC, obtained by heating BC at 60 degrees C in open air for 1 h) may inhibit GJIC. We incubated a human lung cancer cell line (A549) with OBC or BC at 2-10 microM for 5 days. Cell viability (by Trypan-blue assay), GJIC (by scrape-loading dye transfer) and Cx43 expression (by western blotting and immunocytochemical localization) were measured to investigate the effects of OBC and BC on GJIC and the possible mechanisms. The results show that OBC at concentrations lower than 10 microM did not significantly affect cell viability. However, OBC at 5 muM inhibited GJIC, whereas BC at 5 microM markedly increased GJIC. The loss of GJIC in A549 induced by OBC accompanied the aberrant localization and phosphorylation of connexin43 (Cx43). These changes in the expression of Cx43 induced by OBC were similar to those induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter. Thus, our results suggest that in vivo inhibition of GJIC by a high dose of BC on GJIC is, at least in part, attributable to the effect of OBC.

Topics: Adenocarcinoma; Antioxidants; beta Carotene; Blotting, Western; Cell Communication; Cell Line, Tumor; Connexin 43; Fluorescent Dyes; Gap Junctions; Humans; Immunohistochemistry; Indicators and Reagents; Isoquinolines; Lung Neoplasms; Oxidation-Reduction; Phosphorylation

This study examined the relationship between pretrial serum concentrations of retinol, beta-carotene, beta-cryptoxanthin, and lutein/zeaxanthin and the subsequent risk of developing esophageal squamous cell carcinoma and gastric cardia or non-cardia adenocarcinoma in subjects selected from a randomized nutritional intervention trial in Linxian, China, a region with epidemic rates of esophageal and gastric cardia cancer.. We used a stratified case-cohort design to select cohort members for inclusion in this study. In all we measured serum concentrations of the above vitamins in 590 esophageal, 395 gastric cardia, and 87 gastric non-cardia case subjects as well as in 1053 control subjects. Relative risks (RRs) were estimated using Cox proportional hazards models.. Median values in our cohort were low for serum retinol (33.6 microg/dl), beta-carotene (4.3 microg/dl), and beta-cryptoxanthin (3.5 microg/dl), but were high for lutein/zeaxanthin (40.0 microg/dl). Gastric cardia cancer incidence fell 10% for each quartile increase in serum retinol (RR = 0.90, 95% CI = 0.83-0.99). For esophageal cancer, an inverse association with retinol levels was found only in male non-smokers (RR = 0.79 per quartile increase, 95% CI = 0.63-0.99). For gastric non-cardia cancer, an inverse association was limited to subjects 50 years old or younger (RR = 0.58 per quartile, 95% CI = 0.31-0.96). For beta-cryptoxanthin there was a borderline significant protective association for gastric non-cardia cancer (RR = 0.88 per quartile, 95% CI = 0.76-1.0). In contrast, we found the incidence of gastric non-cardia cancer increased (RR = 1.2 per quartile, 95% CI = 1.0-1.3) with increasing concentration of serum lutein/zeaxanthin.. In this population, we found that low retinol and high lutein/zeaxanthin concentrations increased the risks of gastric cardia and gastric non-cardia cancer respectively. We found that there were no strong associations between any of the other analytes and any of the cancer sites.

Topics: Adenocarcinoma; Adult; Aged; beta Carotene; Carcinoma, Squamous Cell; China; Cryptoxanthins; Esophageal Neoplasms; Female; Humans; Lutein; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Regression Analysis; Risk Factors; Stomach Neoplasms; Vitamin A; Xanthophylls; Zeaxanthins

In this study, we examined possible mechanisms of caspase activation during carotenoid-induced apoptosis in tumor cells. We found that beta-Carotene induces apoptosis by the activation of caspase-3 in human leukemia (HL-60), colon adenocarcinoma (HT-29) as well as melanoma (SK-MEL-2) cell lines. This activation is dose dependent and follows that of caspase-8 and caspase-9. Although caspase-8 cleavage is an early event, reaching its maximum activation at 3 h, caspase-9 reaches its maximum activation only at 6 h. The addition of IETD-CHO, a caspase-8-specific inhibitor, completely prevents beta-Carotene-induced apoptosis, whereas only a partial prevention was observed in the presence of LEHD-CHO, a caspase-9-specific inhibitor. beta-Carotene activates caspase-9 via cytochrome c release from mitochondria and loss of mitochondrial membrane potential (Dym). Concomitantly, a dose-dependent decrease in the antiapoptotic protein Bcl-2 and a dose-dependent increase in the cleaved form of BID (t-BID) are observed. Moreover, NF-kB activation is involved in beta-Carotene-induced caspase cascade. These results support a pharmacological role for beta-Carotene as a candidate antitumor agent and show a possible sequence of molecular events by which this molecule may induce apoptosis in tumor cells.

Topics: Adenocarcinoma; Apoptosis; beta Carotene; BH3 Interacting Domain Death Agonist Protein; Carrier Proteins; Caspase 3; Caspase 8; Caspase 9; Caspases; Colonic Neoplasms; Cytochromes c; Enzyme Activation; Enzyme Inhibitors; HL-60 Cells; Humans; Melanoma; Membrane Potentials; Mitochondria; Neoplasms; NF-kappa B; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured

Although the pharmacological role of beta-carotene in the prevention and treatment of colon cancer has received increasing attention, little is known about the molecular mechanisms of action of this carotenoid. The present study demonstrates that beta-carotene, a natural pigment widely present in fruit and vegetables, inhibits the growth of several human colon adenocarcinoma cell lines (COLO 320 HSR, LS-174, HT-29 and WiDr) by inducing cell cycle arrest in G(2)/M phase and apoptosis. These effects were dose and time dependent and strictly related to cell ability to accumulate the carotenoid. COLO 320 HSR cells incorporated beta-carotene to a greater extent than LS-174, HT-29 and WiDr cells and, concomitantly, they exhibited a higher sensitivity to the growth inhibitory effects of the carotenoid. At inhibitory concentrations beta-carotene reduced the expression of cyclin A, a key regulator of G(2)/M progression. Neither p21 nor p27, two cyclin kinase inhibitors, were significantly modified by carotenoid treatment. With respect to apoptosis induction, decreased levels of the apoptosis blocking proteins Bcl-2 and Bcl-xL were also observed. On the other hand, no changes in expression of the apoptosis promoter protein Bax were detected. This study represents a novel aspect of the biological profile of beta-carotene and a new step in elucidating the underlying molecular mechanisms of its antitumor action. In addition, since cell growth inhibitory effects were reached at beta-carotene concentrations achievable in vivo following its supplementation, this study provides a rational approach for the use of beta-carotene in colon cancer.

Topics: Adenocarcinoma; Apoptosis; beta Carotene; Cell Cycle; Cell Cycle Proteins; Cell Division; Colonic Neoplasms; Cyclin A; Down-Regulation; Flow Cytometry; Humans; Immunohistochemistry; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured

This is the first report demonstrating a relationship between apoptosis induction and changes of intracellular redox potential in the growth-inhibitory effects of high concentrations of beta-carotene in a tumor cell line. beta-Carotene inhibited the growth of human WiDr colon adenocarcinoma cells in a dose- and time-dependent manner, induced apoptosis, and blocked Bcl-2 expression. These effects were accompanied by an enhanced production of intracellular reactive oxygen species (ROS). The addition of the antioxidant alpha-tocopherol blocked both the pro-oxidant and the growth-inhibitory effects of the carotenoid. These findings suggest that beta-carotene may act as an inductor of apoptosis by its pro-oxidant properties.

Topics: Adenocarcinoma; Antioxidants; Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; beta Carotene; Cell Division; Cell Survival; Colonic Neoplasms; Dose-Response Relationship, Drug; Free Radicals; Growth Inhibitors; Humans; Oxidants; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Reactive Oxygen Species; Tumor Cells, Cultured; Vitamin E

The purpose of this study is to examine the carotenoid effects on lung tumorigenesis induced by intratracheal instillation of diesel exhaust particles (DEP) into mice weekly for 20 wk. It was suggested that active oxygen radicals might play an important role in DEP-induced lung tumorigenesis. Mice were divided to 4 groups of diet containing 0.02% of palm oil carotene, 0.02% of beta-carotene, or no carotenoid with or without DEP. The BF group (4% fat) and the HF group (16% fat) were prepared for each diet group. The experimental period was 12 mo. By the administration of palm oil carotene, neither adenocarcinoma nor adenoma was found in the BF group. In the HF group with palm oil carotene, no adenocarcinoma was observed, and adenoma was reduced. Adenoma in the HF group was not greatly reduced by beta-carotene, but rather increased in the BF group. No adenocarcinoma was found in either the BF or the HF groups with beta-carotene. The 8-hydroxydeoxyguanosine/deoxyguanosine ratio in palm carotene groups was lower than in the other groups, while that in beta-carotene groups was not. From these results, palm oil carotene was suggested to prevent lung tumorigenesis by its protective effect on DNA from active oxygen. Beta-carotene was supposed to have different effects from palm oil carotene on lung tumorigenesis. Besides the chemopreventive effect, the growth of mice was inhibited by the administration of palm oil carotene. Further studies are necessary to elucidate the mechanisms of carotenoid effects.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenocarcinoma; Adenoma; Animals; Antioxidants; beta Carotene; Carotenoids; Deoxyguanosine; Dietary Fats; DNA Damage; Growth; Lung; Lung Neoplasms; Male; Mice; Mice, Inbred ICR; Reactive Oxygen Species; Time Factors; Vehicle Emissions; Vitamins

Carotenoids have numerous biological properties that may underpin a role for them as chemopreventive agents. However, except for beta-carotene, little is known about how dietary carotenoids are associated with common cancers, including colon cancer.. The objective of this study was to evaluate associations between dietary alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin and the risk of colon cancer.. Data were collected from 1993 case subjects with first primary incident adenocarcinoma of the colon and from 2410 population-based control subjects. Dietary data were collected from a detailed diet-history questionnaire and nutrient values for dietary carotenoids were obtained from the US Department of Agriculture-Nutrition Coordinating Center carotenoid database (1998 updated version).. Lutein was inversely associated with colon cancer in both men and women [odds ratio (OR) for upper quintile of intake relative to lowest quintile of intake: 0.83; 95% CI: 0.66, 1.04; P = 0.04 for linear trend]. The greatest inverse association was observed among subjects in whom colon cancer was diagnosed when they were young (OR: 0.66; 95% CI: 0.48, 0.92; P = 0.02 for linear trend) and among those with tumors located in the proximal segment of the colon (OR: 0.65; 95% CI: 0.51, 0.91; P < 0.01 for linear trend). The associations with other carotenoids were unremarkable.. The major dietary sources of lutein in subjects with colon cancer and in control subjects were spinach, broccoli, lettuce, tomatoes, oranges and orange juice, carrots, celery, and greens. These data suggest that incorporating these foods into the diet may help reduce the risk of developing colon cancer.

Topics: Adenocarcinoma; Age Factors; Aged; Anticarcinogenic Agents; beta Carotene; Carotenoids; Colonic Neoplasms; Cryptoxanthins; Diet; Diet Surveys; Humans; Lutein; Lycopene; Middle Aged; Phytotherapy; Risk Factors; Smoking; Utah; Vegetables; Xanthophylls; Zeaxanthins

We have examined the role of dietary patterns and specific dietary nutrients in the etiology of lung cancer among non-smokers using a multicenter case-control study.. 506 non-smoking incident lung cancer cases were identified in the eight centers along with 1045 non-smoking controls. Dietary habits were assessed using a quantitative food-frequency questionnaire administered by personal interview. Based on this information, measures of total carotenoids, beta-carotene and retinol nutrient intake were estimated.. Protective effects against lung cancer were observed for high consumption of tomatoes, (odds ratio (OR) = 0.5; 95% confidence interval (CI) 0.4-0.6), lettuce (OR = 0.6; 95% CI 0.3-1.2), carrots (OR = 0.8; 95% CI 0.5-1.1), margarine (OR = 0.7; 95% CI 0.5-0.8) and cheese (OR = 0.7; 95% CI 0.5-1.0). Only weak protective effects were observed for high consumption of all carotenoids (OR = 0.8; 95% CI 0.6-1.0), beta-carotene (OR = 0.8; 95% CI 0.6-1.1) and retinol (OR = 0.9; 95% CI 0.7-1.1). Protective effects for high levels of fruit consumption were restricted to squamous cell carcinoma (OR = 0.7; 95% CI 0.4-1.2) and small cell carcinoma (OR = 0.7; 95% CI 0.4-1.2), and were not apparent for adenocarcinoma (OR = 0.9; 95% CI 0.6-1.3). Similarly, any excess risk associated with meat, butter and egg consumption was restricted to squamous and small cell carcinomas, but was not detected for adenocarcinomas.. This evidence suggests that the public health significance of increasing vegetable consumption among the bottom third of the population would include a reduction in the incidence of lung cancer among lifetime non-smokers by at least 25%, and possibly more. A similar protective effect for increased fruit consumption may be present for squamous cell and small cell lung carcinomas.

Topics: Adenocarcinoma; Adult; Aged; beta Carotene; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; Diet; Female; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Public Health; Smoking; Vegetables; Vitamin A

Epidemiologic and animal studies provide support for a relationship between high intakes of carotenoids from fruits and vegetables with reduced risk of several malignancies including prostate cancer. The highly controlled environments of in vitro systems provide an opportunity to investigate the cellular and molecular effects of carotenoids. The effects of beta-carotene (BC) on in vitro growth rates, p21(WAF1) and p53 gene expression, as well as the conversion of BC to retinol were investigated in three human prostate adenocarcinoma cell lines: PC-3, DU 145 and LNCaP. In these experiments, media concentrations of 30 micromol BC/L for 72 h significantly (P < 0.05) slowed in vitro growth rates in all three cell lines, independently of p53 or p21(WAF1) status or expression. (14)C-labeled retinol was detected in prostate tumor cells incubated with (14)C-labeled BC, suggesting metabolic conversion of BC to retinol. Conversely, no (14)C-labeled retinol was detected in media incubated without prostate cancer cells. These studies support a hypothesis that in vitro biological effects of BC on prostate cells may result in part from the conversion of BC to retinol or other metabolites. The possibility that prostate cancer cells in vivo locally metabolize provitamin A carotenoids to retinol and other related metabolites may have implications for our understanding of prostate cancer etiology and the design of future prevention studies.

Topics: Adenocarcinoma; beta Carotene; Cell Division; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Humans; Intracellular Fluid; Male; Prostatic Neoplasms; Tumor Cells, Cultured; Tumor Suppressor Protein p53; Vitamin A

In spite of diverging incidence trends, subsite, and subtype-specific gastric cancer data on the association with dietary antioxidants are sparse. We aimed to test whether the apparent protective effect of antioxidants is mainly confined to noncardia (distal) cancer of the intestinal subtype, to which most of the incidence decline in gastric cancer has been ascribed. In a Swedish study base (total population 1.3 million), we interviewed 567 cases uniformly classified to subsite (cardia vs. noncardia) and subtype (intestinal vs. diffuse), and 1165 population-based controls, frequency matched for age and sex. Serologic data on H. pylori status was available for a subset of 542 individuals. Ascorbic acid (vitamin C) was inversely associated with all subsites and subtypes of gastric cancer in a significant dose-response manner (all p<0.05), with risk reductions between 40% and 60%. beta-carotene was also strongly and negatively associated with risk, particularly with the intestinal type. The associations with alpha-tocopherol (vitamin E) were less clear. The highest parallel intake of all three antioxidants (quartiles 4), compared to those with the lowest parallel intakes (quartiles 1), was associated with a 70% lower risk of developing noncardia cancer (OR 0.3, 95% CI 0.1-0.9). Our results suggest that antioxidants might be especially beneficial among subjects at increased risk for gastric cancer such as smokers and those infected by H. pylori. We conclude that a high intake of antioxidants, as a consequence of high consumption of fruit and vegetables, may lower the risk not only for gastric cancer of the intestinal type, but also for diffuse type adenocarcinoma and cardia cancer.

Topics: Adenocarcinoma; Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Cardia; Case-Control Studies; Female; Fruit; Helicobacter pylori; Humans; Intestinal Neoplasms; Male; Middle Aged; Odds Ratio; Risk Factors; Smoking; Stomach Neoplasms; Sweden; Vegetables; Vitamin E

Cell culture systems provide an opportunity to evaluate the effects of carotenoids on molecular and cellular processes involved in proliferation and differentiation of prostate cancer cells. The stability and cellular uptake of beta-carotene (BC) by prostate cancer cells were investigated in vitro by use of various delivery methods and three human prostate adenocarcinoma cell lines: PC-3, DU 145, and LNCaP. Recovery of BC from the media (prepared from water-dispersible BC beadlets) significantly (p < 0.05) decreased after 12 hours in culture and continued to significantly decrease (p < 0.05) after 24, 48, 72, and 96 hours, an observation primarily attributed to BC degradation rather than isomerization, metabolism, or cellular uptake. The uptake of BC by prostate cancer cells was compared when delivered by tetrahydrofuran, BC-enriched bovine serum, water-dispersible BC beadlets, and artificial liposomes. Recovery of BC after three days in culture from enriched bovine serum medium was significantly (p < 0.05) greater than recovery from medium prepared by beadlets, tetrahydrofuran, or artificial liposomes. We conclude that BC is relatively unstable in vitro and that degradation products may contribute to biological responses. Furthermore, our studies indicate that enriched bovine serum provides a stable and physiological approach to carotenoid treatment of cells in culture.

Topics: Adenocarcinoma; Animals; beta Carotene; Cattle; Culture Media; Drug Delivery Systems; Drug Stability; Furans; Humans; In Vitro Techniques; Lipoproteins; Liposomes; Male; Microspheres; Pharmaceutical Vehicles; Prostatic Neoplasms; Solvents; Time Factors; Tumor Cells, Cultured

Antioxidant vitamins have attracted considerable attention in previous studies of esophageal squamous-cell carcinoma, but dietary studies of adenocarcinoma of the esophagus and gastric cardia remain sparse. Treating these tumors as distinct diseases, we studied intakes of vitamin C, beta-carotene and alpha-tocopherol in a nationwide population-based case-control study in Sweden, with 185, 165, and 258 cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma, and gastric cardia adenocarcinoma, respectively, and 815 controls. Subjects with a high parallel intake of vitamin C, beta-carotene, and alpha-tocopherol showed a 40-50% decreased risk of both histological types of esophageal cancer compared with subjects with a low parallel intake. Antioxidant intake was not associated with the risk of gastric cardia adenocarcinoma. Separately, vitamin C and beta-carotene reduced the risk of esophageal cancers more than alpha-tocopherol. We found that antioxidant intake is associated with similar risk reductions for both main histological types of esophageal cancer. Our findings indicate that antioxidants do not explain the diverging incidence rates of the 2 histological types of esophageal cancer. Moreover, our data suggest that inverse associations with esophageal squamous-cell carcinoma and adenocarcinoma may be stronger among subjects under presumed higher oxidative stress due to smoking or gastroesophageal reflux, respectively. Our results may be relevant for the implementation of focused, cost-effective preventive measures.

Topics: Adenocarcinoma; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carcinoma, Squamous Cell; Cardia; Case-Control Studies; Diet; Dietary Supplements; Drug Synergism; Esophageal Neoplasms; Female; Gastroesophageal Reflux; Humans; Male; Multivariate Analysis; Oxidative Stress; Risk Factors; Smoking; Stomach Neoplasms; Sweden; Vitamin E

We have reported protective effects of dietary administration of a powder "CHRP" containing high amounts of beta-cryptoxanthin and hesperidin prepared from a Satsuma mandarin (Citrus unshiu Marc.) juice on azoxymethane (AOM)-induced rat aberrant crypt foci through suppression of crypt cell proliferation and/or induction of detoxifying enzymes. In the present study, we investigated the modifying effects of a commercial Satsuma mandarin (Citrus unshiu Marc.) juice (MJ) and those of MJ2 and MJ5, which were prepared from MJ and are richer in beta-cryptoxanthin and hesperidin than MJ, on the occurrence of colonic tumors induced by AOM in male F344 rats. Rats were given 2 weekly s.c. injections of AOM (20 mg/kg body weight) to induce colonic neoplasms. They also received MJ, MJ2, or MJ5 as a drinking water at night for 36 weeks, starting 1 week after the last dosing of AOM. AOM exposure produced colonic adenocarcinoma with an incidence of 69% and a multiplicity of 0.76 +/- 0.57/rat at week 38. MJ, MJ2, and MJ5 administration significantly reduced the frequency of colonic carcinoma [MJ: 35% (49% reduction), p < 0.02; MJ2: 20% (64% reduction), p = 0.0028; and MJ5: 15% (78% reduction), p < 0.00021] and multiplicity [MJ: 0.40 +/- 0.58 (47% reduction), p < 0.05; MJ2: 0.25 +/- 0.43 (67% reduction), p < 0.005; and MJ5: 0.15 +/- 0.36 (80% reduction), p < 0.001]. Also, the numbers of cancer cells positive for proliferative cell nuclear antigen (PCNA) and cyclin D1 in colonic tumors were lowered by these treatments. In addition, treatment with MJ, MJ2, or MJ5 significantly increased apoptotic index in colonic adenocarcinoma. These findings might suggest effective chemopreventive ability of MJs, especially MJ5, in colon tumorigenesis.

Topics: Adenocarcinoma; Adenoma; Animals; Anticarcinogenic Agents; Apoptosis; Azoxymethane; beta Carotene; Beverages; Carcinogens; Citrus; Colonic Neoplasms; Cryptoxanthins; Cyclin D1; Hesperidin; Male; Proliferating Cell Nuclear Antigen; Rats; Rats, Inbred F344; Xanthophylls

The effects of combinations between eicosapentaenoic acid (EPA) and beta-carotene on cell growth and lipid peroxidation were investigated in human WiDr colon adenocarcinoma cells. EPA alone was able to inhibit the growth of WiDr cells in a dose- and time-dependent manner. Such an inhibition involved fatty acid peroxidation, as shown by the remarkable increase in the levels of Malondialdehyde (MDA) in EPA-treated cells. Beta-carotene was capable of reducing the growth inhibitory effects of EPA and the levels of MDA in a dose- and a time-dependent manner. In addition, EPA increased beta-carotene consumption in WiDr cells. This study provides evidence that beta-carotene can antagonize the effects of EPA on colon cancer cell growth and lipid peroxidation.

Topics: Adenocarcinoma; beta Carotene; Cell Division; Colonic Neoplasms; Eicosapentaenoic Acid; Humans; Kinetics; Lipid Peroxidation; Malondialdehyde; Time Factors; Tumor Cells, Cultured

Several retrospective and prospective epidemiological investigations have demonstrated that a diet rich in carotenoids could prevent the development of pre-cancerous and neoplastic lesions of the digestive tract. The aim of this examination was to analyse the correlation between colorectal polyps with different histological classifications and serum carotenoid levels.. A 10 ml blood sample was taken from all of the patients after the colonoscopic diagnosis. The serum levels of vitamin A, lutein, zeaxanthin, alpha- and beta-cryptoxanthin, alpha- and beta-carotene were measured in patients with adenomatous colorectal polyp (n = 59, 35 males, 24 females) by high-pressure liquid chromatography (HPLC) and compared with those in healthy subjects (n = 20, 10 males, 10 females). The patients were separated into four groups depending on their histological findings.. The serum levels of vitamin A and zeaxanthin were significantly lower in all patients with polyps (vitamin A: 0.913 +/- 0.112 micromol/l, zeaxanthin: 0.071 +/- 0.012 micromol/l) than in the control healthy group (vitamin A: 2.036 +/- 0.354 micromol/l, zeaxanthin: 0.138 +/- 0.048 micromol/l). The lowest levels were found in patients with focal adenocarcinoma in the polyp. There were no significant differences in the serum levels of other carotenoids. The serum levels of cholesterol, haemoglobin, total protein and albumin were normal in these patients.. There are close and inverse correlations between the serum level of carotenoids and colorectal polyps with different histological grades. The low mean carotenoid levels in patients with adenocarcinoma in the polyp indicate that deficiency of carotenoids may be an important factor in the development of colorectal cancer.

Topics: Adenocarcinoma; Adenomatous Polyps; beta Carotene; Blood Proteins; Carotenoids; Cholesterol; Chromatography, High Pressure Liquid; Colonic Polyps; Colonoscopy; Cryptoxanthins; Female; Hemoglobins; Humans; Intestinal Polyps; Lutein; Male; Middle Aged; Rectal Neoplasms; Serum Albumin; Vitamin A; Xanthophylls; Zeaxanthins

To examine the protective role of dietary antioxidants (carotenoids, vitamin C, vitamin E, glutathione, and flavonoids) in lung cancer risk, a case-control study involving 541 cases of lung cancer and 540 hospitalized controls was carried out in Uruguay. The relevant variables were energy adjusted using the residuals method and then categorized in quartiles. Adjusted odds ratios (ORs) for antioxidants were calculated through unconditional logistic regression. With the exception of lycopene and vitamin C, the remaining antioxidants were associated with significant reductions in risk of lung cancer. Of particular interest was the inverse association between dietary glutathione and lung cancer [OR of quartile with highest intake compared with lowest quartile = 0.42, 95% confidence interval (CI) = 0.27-0.63]. Also, carotenoids and vitamin E were associated with significant reductions in risk of lung cancer (OR = 0.43, 95% CI = 0.29-0.64 for total carotenoids and OR = 0.50, 95% CI = 0.39-0.85 for vitamin E). A joint effect for high vs. low intakes of beta-carotene and glutathione was associated with a significant reduction in risk (OR = 0.32, 95% CI = 0.22-0.46). It could be concluded that dietary antioxidants are associated with a significant protective effect in lung carcinogenesis and that the inverse association for glutathione persisted after controlling for total vegetables and fruits.

Topics: Adenocarcinoma; Adult; Age Distribution; Aged; Aged, 80 and over; Antioxidants; beta Carotene; Carcinoma; Carcinoma, Large Cell; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Case-Control Studies; Diet; Glutathione; Humans; Logistic Models; Lung Neoplasms; Male; Middle Aged; Odds Ratio; Risk Factors; Surveys and Questionnaires; Uruguay

Most studies concerning a possible protective role of carotenoids against cancer focus on serum carotenoid levels. We have used Raman microspectroscopy to study the intracellular amounts of carotenoids in lymphocytes of lung cancer patients and of healthy individuals. Our results indicate a significant decrease of carotenoids in lung carcinoma patients compared with healthy individuals, particularly in adenocarcinoma patients. Carotenoid supplementation raised the serum concentration in 2 lung cancer patients up to normal levels, whereas intracellular content remained significantly lower. This indicates that carotenoid uptake by lymphocytes is not only dependent on serum carotenoid concentration. Our findings indicate that Raman microspectroscopy, a recently developed technique to measure intracellular levels of drugs, is also well suited to obtain quantitative data on carotenoid amounts inside cells.

Topics: Adenocarcinoma; Adult; Age Factors; Aged; beta Carotene; Carotenoids; Chromatography, High Pressure Liquid; Cryptoxanthins; Food, Fortified; Humans; Lung Neoplasms; Lycopene; Lymphocytes; Reference Values; Spectrum Analysis, Raman; Xanthophylls

Lower lobe origin and histologic diagnosis of adenocarcinoma have been described as useful parameters for attributing lung cancer to prior asbestos exposure. To assess whether these characteristics differed between asbestos-exposed individuals and smokers, we evaluated lobe of origin and histologic type of tumors in 78 asbestos-exposed and 214 nonexposed heavy smokers developing lung cancer during the Carotene and Retinol Efficacy Trial (CARET), a prospective cancer chemoprevention trial. Most tumors in both cohorts, regardless of radiographic fibrosis at baseline, originated in upper lobes, representing 67% in asbestos-exposed and 80% in smokers, respectively (adjusted OR for lower lobe = 1.41; 95% CI = 0.69-2.91). Adenocarcinoma represented 32% of lung tumors in the asbestos cohort, and 30% in the smoking cohort (adjusted OR = 0.78; 95% CI = 0.40-1.55), and was inversely associated with radiographic fibrosis (adjusted OR = 0.19; 95% CI = 0.06-0.62). We conclude that neither anatomic site nor histologic cell type of tumors distinguishes effectively between smoking and asbestos as causal factors in development of lung cancer.

Topics: Adenocarcinoma; Anticarcinogenic Agents; beta Carotene; Causality; Confounding Factors, Epidemiologic; Diterpenes; Double-Blind Method; Female; Humans; Lung Neoplasms; Male; Middle Aged; Multicenter Studies as Topic; Occupational Diseases; Occupational Exposure; Prospective Studies; Pulmonary Fibrosis; Randomized Controlled Trials as Topic; Retinyl Esters; Smoking; Vitamin A

The effects of vitamins E and E, beta-carotene and selenium on development of N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic tumours in hamsters were investigated. Dietary supplementation of vitamin C, alone as well as in combination with beta-carotene resulted in consistently lower numbers of advanced ductular lesions. The differences with the controls, however, did not reach the level of statistical significance. Beta-Carotene alone demonstrated no inhibitory effect on the development of (pre)neoplastic lesions in the pancreas. Vitamin E or Se, either alone or in combination, had no effect on the development of advanced ductular lesions in BOP-treated hamsters.

Topics: Adenocarcinoma; Animals; Ascorbic Acid; beta Carotene; Body Weight; Carcinogens; Carcinoma, Ductal, Breast; Carotenoids; Cricetinae; Diet; Male; Mesocricetus; Nitrosamines; Organ Size; Pancreatic Neoplasms; Selenium; Vitamin E

In order to discover the relationship between dietary nutrients intake and risk of lung cancer 1:1 matched case-control study on 156 recent histologiclly diagnosed primary lung cancer patients and 156 patients with respiratory tumour and other related diseases as controls, was conducted in Wuhan. All cases and controls were asked to participate in the nutritional assessment program and a food frequency questionnaire containing 64 food items was filled in. The findings showed that there was a statistically significant difference between dietary intake of beta-carotene between the two groups (2877.13 +/- 393.43 vs. 3445 +/- 430.98 micrograms/day). Having controled the confounding factor of cigarette smoking, a significant linear trend for lower dietary carotene intake toward higher lung cancer risk was observed.

Topics: Adenocarcinoma; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; China; Diet; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nutrition Surveys; Risk Factors; Smoking

The relationship between risk of prostate cancer and dietary intake of energy, fat, vitamin A, and other nutrients was investigated in a case-control study conducted in Ontario, Canada. Cases were men with a recent, histologically confirmed diagnosis of adenocarcinoma of the prostate notified to the Ontario Cancer Registry between April 1990 and April 1992. Controls were selected randomly from assessment lists maintained by the Ontario Ministry of Revenue, and were frequency-matched to the cases on age. The study included 207 cases (51.4 percent of those eligible) and 207 controls (39.4 percent of those eligible), and information on dietary intake was collected from them by means of a quantitative diet history. There was a positive association between energy intake and risk of prostate cancer, such that men at the uppermost quartile level of energy intake had a 75 percent increase in risk. In contrast, there was no clear association between the non-energy effects of total fat and monounsaturated fat intake and prostate cancer risk. There was some evidence for an inverse association with saturated fat intake, although the dose-response pattern was irregular. There was a weak (statistically nonsignificant) positive association between polyunsaturated fat intake and risk of prostate cancer. Relatively high levels of retinol intake were associated with reduced risk, but there was essentially no association between dietary beta-carotene intake and risk. There was no alteration in risk in association with dietary fiber, cholesterol, and vitamins C and E. Although these patterns were evident both overall and within age-strata, and persisted after adjustment for a number of potential confounding factors, they could reflect (in particular) the effect of nonrespondent bias.

Topics: Adenocarcinoma; Aged; beta Carotene; Carotenoids; Case-Control Studies; Diet; Dietary Fats; Energy Intake; Humans; Male; Middle Aged; Prostatic Neoplasms; Risk Factors; Vitamin A

Beta-carotene at concentration of 6.25 micrograms/ml was shown to inhibit significantly the colony forming efficiency (CFE) of cultured human lung cancer 801 cell line and at 12.5 micrograms/ml was shown to completely inhibit CFE. A 42%-68% (P < 0.01) decrease in spontaneous lung metastasis of LA795 murine pulmonary adenocarcinoma was observed when T739 inbred strain mice were fed a diet with beta-carotene (25mg/100g diet). Ability of DNA and RNA synthesis of lung cancer cells were decreased (P < 0.05) after treating with beta-carotene (25 micrograms/ml) by 24 hours, but the ability for DNA synthesis of human lymphocytes was not effected by the same treatment. Expression of ras oncogene was proved to be inhibited by beta-carotene because the product of ras p21 proteins of cancer cells was decreased after treating by beta-carotene.

Topics: Adenocarcinoma; Animals; beta Carotene; Carotenoids; DNA, Neoplasm; Genes, ras; Humans; Lung Neoplasms; Mice; Oncogene Protein p21(ras); RNA, Neoplasm; Tumor Cells, Cultured; Tumor Stem Cell Assay

Selenium has been suggested to be anticarcinogenic and to play a role in the cellular defense against oxidative stress. The association between toenail selenium (a marker of long-term selenium status) and lung cancer was investigated in a cohort study of diet and cancer that started in 1986 among 120,852 Dutch men and women aged 55-69 years. After 3.3 years of follow-up, 550 incident cases of lung carcinoma were detected. Toenail selenium data were available for 370 lung cancer cases and 2459 members of a randomly selected subcohort. The rate ratio of lung cancer for subjects in the highest compared to the lowest quintile of toenail selenium, after controlling for age, gender, smoking, and education, was 0.50 (95% confidence interval, 0.30-0.81), with a significant inverse trend across quintiles (P = 0.006). The protective effect of selenium was concentrated in subjects with a relatively low dietary intake of beta-carotene or vitamin C. The rate ratio in the highest compared to the lowest quintile of selenium was 0.45 in the low beta-carotene group (95% confidence interval, 0.22-0.92; trend P = 0.028) and 0.36 in the low vitamin C group (95% confidence interval, 0.17-0.75; trend P < 0.001). The results of this study support an inverse association between selenium status and lung cancer and suggest a modification of the effect of selenium by the antioxidants beta-carotene and vitamin C.

Topics: Adenocarcinoma; Age Factors; Aged; Ascorbic Acid; beta Carotene; Carcinoma; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Carotenoids; Cohort Studies; Education; Feeding Behavior; Female; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Nails; Netherlands; Prospective Studies; Risk Factors; Selenium; Sex Factors; Smoking; Surveys and Questionnaires; Time Factors; Toes; Vitamin A

In a case-control study to determine the risk of developing lung cancer, the serum levels of vitamins A and E, carotene and selenium were determined in 31 patients, newly diagnosed as having lung cancer, and in matched controls, the said controls being selected from outpatients with no cancer. A significant, inverse association was found between serum vitamins A and E and lung cancer. The relative risk for the low vs high tertiles were, respectively, 5.94 for serum vitamin A and 8.44 for serum vitamin E. Taking histological cancer subtype into account, no relation was revealed between the microelements and squamous cell carcinoma of the lung. The relative risk for lung cancer was 6.50, however, when three, or all four, microelement levels were in the lowest tertile, compared with there being fewer than three in the lowest tertile. Even when three microelements, excluding vitamin E which had the most significant inverse association with lung cancer, were considered, the relative risk was 7.50 when any two or all three were in the lowest tertile, compared with there being just one microelement or none at all in the lowest tertile. A combined effect of vitamins A and E, carotene and selenium on the development of lung cancer has, therefore, been suggested. Further studies will thus be necessary to elucidate the cumulative effect of the serum micronutrients and trace elements, as well as the effect of single elements, on the development of lung cancer.

Topics: Adenocarcinoma; Adult; Aged; beta Carotene; Carcinoma; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Risk Factors; Selenium; Smoking; Vitamin A; Vitamin E

The hypothesis that dietary cholesterol is positively associated with lung cancer was investigated in a 24-year cohort study of 1,878 middle-aged men who were employed in 1958 by the Western Electric Company in Chicago. The relative risk of lung cancer associated with an increment in dietary cholesterol of 500 mg/day was 1.9 (95 percent confidence interval 1.1-3.4) after adjustment for cigarettes, age, and intake of beta-carotene and fat. Results suggested that the association was specific to cholesterol from eggs. Further research is needed to understand the basis for this association.

Topics: Adenocarcinoma; Adult; beta Carotene; Carcinoma, Squamous Cell; Carotenoids; Chicago; Cholesterol, Dietary; Cohort Studies; Dietary Fats; Eggs; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Risk; Smoking

A unique case-control study design including family members of cases and controls was used to assess the association between serum beta-carotene and cancer. The cases (n = 389) were incident cancer cases diagnosed between 1981 and 1984 in Wellington, New Zealand, and the controls (n = 391) were hospital patients without cancer. Both cases and controls were on a home diet at the time beta-carotene levels were measured. Since findings concerning patients who have already been diagnosed with cancer may reflect changes that occurred subsequent to development of cancer, family members of cancer patients (n = 618) and control patients (n = 675) were included, giving a total of 2,073 study participants. Low levels of beta-carotene were observed for individuals with a number of cancers, including cancers of the lung stomach, esophagus, small intestine, cervix, and uterus. Low levels of beta-carotene were also found in the relatives of these cancer patients. These differences persisted after stratification by current cigarette smoking. The strongest findings were those for lung cancer. Excluding adenocarcinoma, lung cancer patients had average serum beta-carotene levels of 40.2 micrograms/dl, 25.9 micrograms/dl lower than those of controls, adjusted for age, sex, and length of sample storage (p less than 0.01). Family members of the lung cancer patients also had lower values than family members of control patients, with an adjusted difference of 10.8 micrograms/dl (p less than 0.01). Odds ratio estimates for lung cancer by quartiles of beta-carotene residuals ranged from 3.6 (90% confidence interval (CI) 1.1-12.2) for the second-highest quartile to 6.6 (90% CI 1.9-23.0) for the lowest quartile (test for trend, p less than 0.001). Patients with cancers of the breast, colon, prostate, and skin did not have lower levels of serum beta-carotene than expected. Family members of individuals with these cancers also did not have lower levels of serum beta-carotene. The cancer sites that were associated with serum beta-carotene are, in general, sites for which smoking is a strong risk factor, and the sites that were not associated with beta-carotene do not have smoking as a risk factor.

Topics: Adenocarcinoma; Adult; beta Carotene; Carotenoids; Case-Control Studies; Family; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; New Zealand; Smoking

The human intestinal Caco-2 cell line, described as enterocyte-like in a number of studies, was examined for its ability to carry out the metabolism of vitamin A normally required in the absorptive process. Caco-2 cells contained cellular retinol-binding protein II, a protein which is abundant in human villus-associated enterocytes and may play an important role in the absorption of vitamin A. Microsomal preparations from Caco-2 cells contained retinal reductase, acyl-CoA-retinol acyltransferase (ARAT), and lecithin-retinol acyltransferase (LRAT) activities, which have previously been proposed to be involved in the metabolism of dietary vitamin A in the enterocyte. When intact Caco-2 cells were provided with beta-carotene, retinyl acetate, or retinol, synthesis of retinyl palmitoleate, oleate, palmitate, and small amounts of stearate resulted. However, exogenous retinyl palmitate or stearate was not used by Caco-2 cells as a source of retinol for ester synthesis. While there was a disproportionate synthesis of monoenoic fatty acid esters of retinol in Caco-2 cells compared to the retinyl esters typically found in human chylomicrons or the esters normally synthesized in rat intestine, the pattern was consistent with the substantial amount of unsaturated fatty acids, particularly 18:1 and 16:1, found in the sn-1 position of Caco-2 microsomal phosphatidylcholine, the fatty acyl donor for LRAT. Both ARAT and LRAT have been proposed to be responsible for retinyl ester synthesis in the enterocyte.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acyltransferases; Adenocarcinoma; Alcohol Oxidoreductases; beta Carotene; Carotenoids; Cell Line; Colonic Neoplasms; Cytosol; Humans; Kinetics; Microsomes; Retinol O-Fatty-Acyltransferase; Retinol-Binding Proteins; Retinol-Binding Proteins, Cellular; Vitamin A

A case-control study among white women in Los Angeles County was conducted to investigate the role of smoking and other factors in the etiology of lung cancer in women. A total of 149 patients with adenocarcinoma (ADC) and 71 patients with squamous cell carcinoma (SCC) of the lung and their age- and sex-matched controls were interviewed. Personal cigarette smoking accounted for almost all of SCC and about half of ADC in this study population. Among nonsmokers, slightly elevated relative risk(s) (RR) for ADC were observed for passive smoke exposure from spouse(s) [RR = 1.2; 95% confidence interval (Cl) = 0.5, 3.3] and at work (RR = 1.3; 95% Cl = 0.5, 3.3). Childhood pneumonia (RR = 2.7; 95% Cl = 1.1, 6.7) and childhood exposure to coal burning (RR = 2.3; 95% Cl = 1.0, 5.5) were additional risk factors for ADC. For both ADC and SCC, increased risks were associated with decreased intake of beta-carotene foods but not for total preformed vitamin A foods and vitamin supplements.

Topics: Adenocarcinoma; beta Carotene; California; Carotenoids; Dairy Products; Diet; Epidemiologic Methods; Female; Humans; Lung Diseases; Lung Neoplasms; Occupations; Population Surveillance; Risk; Smoking; Tobacco Smoke Pollution; Vitamin A

Male CBA/J mice, ingesting a vitamin A- and beta-carotene-sufficient laboratory chow, were inoculated in a hind limb with 2 X 10(5) C3HBA adenocarcinoma cells. When the mean tumor size was 6.2 mm, the mice were divided randomly into groups; some groups received supplemental vitamin A or beta-carotene, some received 3,000 rad local radiation to the tumor, and others received both radiation and one of the supplements. All mice that received only radiation or one of the dietary supplements died within 3 months. When local irradiation and supplemental vitamin A or beta-carotene were coupled, "complete" tumor regression occurred in every case (12/12), and tumor regrowth in and death of the mice occurred in only 1 of 12 in each of these groups during the succeeding 12 months. One year after irradiation and dietary supplementation, half the surviving mice were switched back to the control chow. During the next year, none of the mice remaining on the vitamin A or beta-carotene supplements developed tumors; however, of 6 mice switched from vitamin A, 5 had tumors that reappeared. In contrast, tumors recurred in only 2 of 6 mice after they were switched from beta-carotene. A second experiment yielded similar results. These results show that both vitamin A and beta-carotene supplementation added remarkably to the antitumor effect of local irradiation. beta-Carotene supplementation produced a greater residual antitumor action than vitamin A supplementation after the supplements were discontinued, which may have been due to greater tissue storage of beta-carotene.

Topics: Adenocarcinoma; Animals; beta Carotene; Carotenoids; Male; Mice; Mice, Inbred DBA; Mice, Inbred Strains; Neoplasms, Experimental; Radiotherapy Dosage; Vitamin A

Topics: Adenocarcinoma; Animals; beta Carotene; Carotenoids; Diet; Male; Mice; Mice, Inbred CBA; Neoplasm Transplantation; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Radiation Dosage; Vitamin A