beta-carotene and Metaplasia

Since a high concentration of beta-carotene in blood reduces the risk of lung cancer, a large-scale intervention examination containing beta-carotene was conducted, mainly by the National Cancer Institute. The results showed that the risk of lung cancer increased with administration of beta-carotene. This result demonstrates that continuation of smoking is an important factor in the increased risk, and not smoking is confirmed to be the most important prevention method. The authors examined the treatment effect of raising the concentration of folic acid and vitamin B12 in blood on bronchial dysplasia as a pre-cancerous lesion. A significant medical treatment effect was see in the folic acid and vitamin B12 medication groups, which seems promising for the chemoprevention of lung cancer.

Topics: beta Carotene; Bronchi; Drug Administration Schedule; Drug Therapy, Combination; Folic Acid; Humans; Lung Neoplasms; Metaplasia; Smoking Cessation; Vitamin B 12

The use of biomarkers is a promising approach to the study of human cancer risk. Bronchial metaplasia in sputum cytology may be a marker for potential premalignancy that can be used for population studies. We recently performed a randomized, controlled trial in smokers on the effect of 14 weeks beta-carotene (20mg/day) on markers for DNA damage. We now have evaluated the application of sputum cytology in this study and performed a preliminary evaluation of the effect of beta-carotene. Of the 150 potential participants in this trial 75 were not eligible because they failed to produce sputum samples (n = 29), or because samples were unsatisfactory (n = 46). The eligible group was older (41 vs 37 years) and had smoked longer (23 vs 19 years), but had similar cigarette consumption (mean 21/day) and plasma cotinine levels. Metaplasia was graded in seven categories. Only 11 subjects (15%) showed minor or mild atypia on study entry. Agreement within and between observers was 95% within the same or an adjacent category. We observed no significant correlation between before and after treatment final metaplasia scores in either the beta-carotene (Spearman R = 0.18, P = 0.3) or placebo group (Spearman R = 0.17, P = 0.3). Initial metaplasia scores were somewhat higher in the beta-carotene group (n = 33) than in the placebo group (n = 42) (P = 0.06). Final metaplasia scores were similar in both groups (P = 0.69), and there was no decrease in metaplasia scores in the beta-carotene group (P = 0.75). This study indicates that sputum cytology may not yet be a readily applicable marker in studies of a healthy asymptomatic population, because many smokers do not spontaneously produce sputum, more severe lesions are rare, and variation over time in the minor lesions in large. Therefore, the preliminary evidence that beta-carotene has no influence should be interpreted with care.

Topics: Adult; beta Carotene; Biomarkers; DNA Damage; Double-Blind Method; Humans; Lung Neoplasms; Male; Metaplasia; Middle Aged; Smoking; Sputum; Statistics, Nonparametric

A randomized chemoprevention trial on precancerous lesions of the stomach is being conducted in Tachira State, Venezuela. The aims of the study are to evaluate the efficacy of vitamin supplementation in preventing the progression rate of precancerous lesions. Here we report on the pilot phase of the study in which two antioxidant preparations were evaluated on their ability to raise antioxidant levels in plasma and in gastric juice. The study aimed also to determine the antibiotic sensitivity profiles of Helicobacter pylori isolates prevalent in the area. Forty-three subjects with precancerous lesions (chronic gastritis, chronic atrophic gastritis, intestinal metaplasia and dysplasia) of the stomach were randomized to one of two antioxidant treatments. Treatment 1 (250 mg of standard vitamin C, 200 mg of vitamin E and 6 mg of beta-carotene three times a day) or treatment 2 (150 mg of standard vitamin C, 500 mg of slow release vitamin C, 75 mg of vitamin E and 15 mg of beta-carotene once a day) for 7 days. Blood levels of total vitamin C, beta-carotene and alpha-tocopherol and gastric juice levels of ascorbic acid and total vitamin C were measured before and after treatment on day 8. Both treatments increased the plasma levels of total vitamin C, beta-carotene and alpha-tocopherol/cholesterol but not those of ascorbic acid or total vitamin C in gastric juice. Treatment 1 was the best choice and resulted in a greater increase in the plasma levels of beta-carotene and alpha-tocopherol. H. pylori was cultured from 90% of the gastric biopsies; 35 isolates were identified which were highly resistant to metronidazole, a front-line antibiotic recommended against H. pylori in other settings.

Topics: Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Carotenoids; Chemoprevention; Chronic Disease; Disease Progression; Female; Gastric Juice; Gastritis; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metaplasia; Middle Aged; Pilot Projects; Precancerous Conditions; Stomach Neoplasms; Venezuela; Vitamin E; Vitamins

Southwest metropolitan Mexico City (SWMMC) inhabitants have been exposed several hours per day for the last 6 years to photochemical smog, ozone being the most important oxidant pollutant. Subjects exposed to the SWMMC atmosphere develop several histopathological changes in their nasal mucosa: dysplasia is the most significant, affecting 78.72% of adult individuals within 60 or more days of residence in SWMMC. This study was originally designed to explore whether chemical intervention could modify nasal dysplasia, as determined by nasal cytology, in a defined adult population. In a placebo-controlled, randomized, double-blind trial, 177 healthy male subjects were divided into 5 groups to whom 5000 IU of vitamin A, 100 IU of vitamin E, a combination of vitamins A and E (5000 IU + 100 IU), 16 mg of beta-carotene, or placebo were administered daily for 4 months. Sixteen clinical and cytological variables were monitored. No effect on dysplasia was seen at the end of the 4-month trial; however, an apparent reversibility as well as progression of the dysplastic nasal lesions and high correlation coefficients between dysplasia and nasal cytology of polymorphonuclear leukocytes (PMNs; 0.85), squamous metaplasia (SM; 0.50), and nasal mucosa atrophy (NMA; 0.41) were found. A mathematical theoretical nasal dysplasia (tD) predictor equation for SWMMC adult male inhabitants is proposed (tD = 0.85 delta PMNs + 0.50 delta SM + 0.41 delta NMA + 0.98), in which PMNs are the best single dysplasia predictor, and all variables are independent.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Atrophy; beta Carotene; Carotenoids; Humans; Male; Metaplasia; Mexico; Middle Aged; Models, Biological; Nasal Mucosa; Nose Diseases; Pilot Projects; Smog; Vitamin A; Vitamin E

Incomplete intestinal metaplasia (IM) is a precursor of stomach cancer. To identify risk factors of incomplete IM, a 2-stage survey was carried out in 1995 among 1,485 residents in Matzu, an area with highest mortality from stomach cancer in Taiwan. There were 312 study subjects including 174 men and 138 women sampled for the gastroendoscopic examination of IM. Information on personal and familial history of stomach cancer, cigarette smoking, alcohol consumption and intake frequency of various salted food items were obtained by personal interview based on a structured questionnaire. Blood samples were collected from each participant. Four biopsies per subject were taken from all subjects at gastroendoscopic examination to diagnose the status of IM pathologically. The Helicobacter pylori in biopsies was detected by the histomorphological or immunochemistry method, and antibodies against H. pylori in serum by the enzyme-linked immunosorbent assay. Plasma level of selenium was determined by atomic absorption spectrometry, plasma level of retinol, alpha-tocopherol, alpha-carotene, and beta-carotene by high performance liquid chromatography, genotypes of glutathione S-transferase (GST) M1 and T1 and cytochrome P450 (CYP) 2E1 by polymerase chain reaction. The significant association between history of stomach cancer among first-degree relatives and incomplete IM was found (odds ratio [OR] = 2.50; 95% confidence interval [CI] = 1.15-5.43). There was no association between H. pylori infection and incomplete IM. Alcohol drinkers for >20 years had an elevated risk compared to non-drinkers (OR = 3.34; 95% CI = 1.19-9.39). No associations between incomplete IM and plasma levels of selenium, retinol, alpha-tocopherol, alpha-carotene and beta-carotene were found. Salted food including salted meat, dehydrated salted vegetables and raw salted seafood consumed at ages of

Topics: Adolescent; Adult; alpha-Tocopherol; beta Carotene; Case-Control Studies; Cytochrome P-450 CYP2E1; Female; Genotype; Glutathione Transferase; Humans; Intestines; Male; Metaplasia; Polymerase Chain Reaction; Polymorphism, Genetic; Risk Factors; Selenium; Sodium, Dietary; Stomach Neoplasms; Taiwan

Topics: Achlorhydria; Ascorbic Acid; beta Carotene; Gastritis, Atrophic; Helicobacter Infections; Helicobacter pylori; Humans; Metaplasia; Phenotype; Precancerous Conditions; Remission Induction; Stomach Neoplasms; Treatment Outcome

Topics: Animals; Anticarcinogenic Agents; Antioxidants; Asbestosis; beta Carotene; Cocarcinogenesis; Cohort Studies; Down-Regulation; Ferrets; Gene Expression Regulation; Genes, fos; Genes, jun; Humans; Incidence; Lung; Lung Neoplasms; Metaplasia; Nicotiana; Plants, Toxic; Proliferating Cell Nuclear Antigen; Receptors, Retinoic Acid; Smoke; Smoking; Transcription Factor AP-1; Tretinoin

Epidemiologic studies have demonstrated that individuals who eat more fruits and vegetables and/or have high levels of serum beta-carotene have a lower risk of cancer, especially lung cancer. However, recent human intervention studies using beta-carotene supplements have shown an increase in the risk of lung cancer among smokers and asbestos workers. In this study, we used an animal model system to evaluate the hazard associated with a combination of high-dose beta-carotene supplementation and tobacco smoking.. Ferrets were given a beta-carotene supplement, exposed to cigarette smoke, or both for 6 months. Cell proliferation and squamous metaplasia in lung tissue were assessed by examination of proliferating-cell nuclear antigen expression and histopathologic examination, respectively. beta-Carotene and retinoid concentrations in lung tissue and plasma samples were analyzed by high-performance liquid chromatography. Expression of genes for retinoic acid receptors (RARs) and activator protein-1 (encoded by the c-Jun and c-Fos genes) in lung tissue specimens was examined by western blotting.. A strong proliferative response in lung tissue and squamous metaplasia was observed in all beta-carotene-supplemented animals, and this response was enhanced by exposure to tobacco smoke. When compared with control groups, all three treatment groups had statistically significantly lower concentrations of retinoic acid in lung tissue, and they exhibited 18%-73% reductions in RARbeta gene expression; however, RARalpha and RARgamma gene expression was not reduced. Ferrets given a beta-carotene supplement and exposed to tobacco smoke had threefold to fourfold elevated expression of the c-Jun and c-Fos genes.. Diminished retinoid signaling, resulting from the suppression of RARbeta gene expression and overexpression of activator protein-1, could be a mechanism to enhance lung tumorigenesis after high-dose beta-carotene supplementation and exposure to tobacco smoke.

Topics: Animals; beta Carotene; Cell Division; Cocarcinogenesis; Diterpenes; Down-Regulation; Environmental Exposure; Ferrets; Gene Expression Regulation; Genes, fos; Genes, jun; Humans; Lung; Lung Neoplasms; Male; Metaplasia; Nicotiana; Plants, Toxic; Precancerous Conditions; Proliferating Cell Nuclear Antigen; Receptors, Retinoic Acid; Retinyl Esters; Signal Transduction; Smoke; Transcription Factor AP-1; Tretinoin; Vitamin A

The study described in this paper was primarily conducted to identify the cell types involved in the formation, progression and regression of metaplastic changes in the respiratory tract epithelium of hamsters after intratracheal intubations with benzo[a]pyrene. Furthermore, the role of vitamin A and beta-carotene in these processes was studied. In the course of the study a remarkable effect of dietary beta-carotene on survival of hamsters became a subject of investigation. Hamsters were fed diets with various levels of vitamin A or beta-carotene and were treated intratracheally with a suspension of benzo[a]pyrene with ferric oxide in saline. The tumour response of the respiratory tract was very low (2.8%) and hyper- and metaplasia of respiratory epithelium were virtually absent. However, an interesting observation was an exceptionally low mortality of only 2% after 69 weeks in the group of hamsters fed a high beta-carotene diet (1% w/w), whereas in the other groups mortality after 69 weeks amounted to 25%. Although the exact cause of death of most of the hamsters could not be established, a 40% reduction of lipid peroxidation in the livers was found in the high beta-carotene group. Moreover, in this group the degree and incidence of nephrosis and of focal mineralization of kidneys and heart were lower than in the other groups. These favourable effects of the high beta-carotene diet may have contributed to the unusually high survival rate in hamsters fed this diet. Further studies are planned to verify and study this observation.

Topics: Animals; Benzo(a)pyrene; beta Carotene; Carotenoids; Cricetinae; Diet; Eating; Epithelium; Ferric Compounds; Intubation, Intratracheal; Liver; Male; Mesocricetus; Metaplasia; Respiratory System; Respiratory Tract Neoplasms; Vitamin A