ascorbic-acid has been researched along with Adenoma* in 30 studies
9 review(s) available for ascorbic-acid and Adenoma
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Effectiveness and safety of 1-L PEG-ASC versus other bowel preparations for colonoscopy: A meta-analysis of nine randomized clinical trials.
A 1-L polyethylene glycol plus ascorbate (PEG-ASC) preparation has been recently developed to improve patients' experience in colonoscopy. This meta-analysis aimed to evaluate the effectiveness and safety of 1-L PEG-ASC compared with those of other bowel preparations for colonoscopy.. MEDLINE, Embase, Scopus, and the Cochrane Library were systematically searched for randomized controlled trials comparing 1-L PEG-ASC with other bowel preparations published through July 2022. A random-effects model was applied for pooling the results; heterogeneity was expressed as I. Nine studies met the inclusion criteria and were included. The analysis showed significantly higher cleansing success (CS) (OR = 1.50; 95% CI = 1.25-1.81; p < 0.01, I. Compared to other preparations, 1-L PEG-ASC yielded higher overall CS, higher right-colon HQC rates, and similar ADR. The number of patients with AEs and incidence of the total AEs were significantly higher with 1-L PEG-ASC in the absence of serious AEs. Topics: Adenoma; Ascorbic Acid; Cathartics; Colonoscopy; Humans; Laxatives; Polyethylene Glycols; Randomized Controlled Trials as Topic | 2023 |
Efficacy of ultra-low volume (≤1 L) bowel preparation fluids: Systematic review and meta-analysis.
High-quality bowel preparation is paramount for the diagnostic accuracy and safety of colonoscopy; however, it is often difficult for patients to adhere to high-volume laxatives, which may contribute to poor bowel preparation. This review aims to assess the efficacy of bowel preparation fluids of 1 L or less (≤1 L).. We performed a systematic review including all relevant randomized controlled trials on ultra-low volume (≤1 L) bowel preparation fluids for colonoscopy published since 2015. Primary endpoint was the percentage of adequately prepared patients. Secondary endpoints included adenoma detection rate (ADR) and safety.. Bowel preparation with sodium picosulfate/magnesium citrate (SPMC; 19 trials, n = 10,287), 1L-polyethylene glycol with ascorbate (PEGA; 10 trials, n = 1717), sodium phosphate (NaP; 2 trials, n = 621), and oral sulfate solution (OSS; 3 trials, n = 597) was adequate in 75.2%, 82.9%, 81.9%, and 92.1%, respectively, of patients; however, heterogeneity between studies was considerable (I. Ultra-low volume bowel preparation fluids do not always meet the 90% quality standard for adequate bowel preparation as defined by current guidelines. Nonetheless, they may be considered in patients intolerant for higher-volume laxatives and without risk factors for inadequate bowel preparation or dehydration-related complications. Topics: Adenoma; Ascorbic Acid; Cathartics; Colonoscopy; Humans; Polyethylene Glycols | 2022 |
Effectiveness and safety of NER1006 versus standard bowel preparations: A meta-analysis of randomized phase-3 clinical trials.
A 1 L PEG-based preparation for colonoscopy (NER1006) has been recently developed.. We conducted a meta-analysis of randomized controlled trials (RCTs) to explore the effectiveness and safety of NER1006 versus traditional preparations.. PubMed/Medline and Embase were systematically searched through January 2020 for phase-3 RCTs comparing NER1006 versus standard preparations.. When compared to traditional preparations, NER1006 showed a better overall cleansing of the colon as well as a greater high-quality cleansing of the right colon, with comparable ADR. A higher incidence of mild to moderate TEAEs was observed for NER1006, in the absence of serious adverse events. Topics: Adenoma; Aged; Ascorbic Acid; Cathartics; Clinical Trials, Phase III as Topic; Colonoscopy; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Polyethylene Glycols; Preoperative Care; Randomized Controlled Trials as Topic | 2020 |
Enhanced instructions improve the quality of bowel preparation for colonoscopy: a meta-analysis of randomized controlled trials.
The success of a colonoscopy is highly dependent on the quality of bowel preparation (BP). Many patients have poor BP due to non-compliance with regular instructions. Reports concerning the effects of enhanced instructions on BP quality are inconsistent. The aim of this meta-analysis was to compare BP quality between patients receiving enhanced instructions in addition to regular instructions and those who received regular instructions only.. MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched to identify relevant studies published for August 2015. The quality of BP (adequate/inadequate), adenoma detection rate, polyp detection rate, willingness to repeat preparation, and adverse events were estimated by using odds ratios (OR) and 95% confidence intervals (CI) with random effects models.. Eight randomized controlled trials (n = 3795) were included. Patients who received enhanced instructions showed significantly better BP quality than those receiving only regular instructions (OR, 2.35; 95% CI, 1.65-3.35; P < .001). Subgroup analysis showed that the beneficial effects of enhanced instructions on BP quality were consistent among patients receiving different purgative types, administration methods, or diet restriction (all P < .05). Patients in the enhanced instructions group showed more willingness to repeat the preparation (OR, 1.91; 95% CI, 1.20-3.04; P = .006).. Enhanced instructions significantly improved the quality of BP and willingness to repeat the preparation in patients undergoing colonoscopy. Factors related to patient instructions appear to be as important as the preparation method itself in improving BP quality. Topics: Adenoma; Ascorbic Acid; Cathartics; Cecum; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Diet; Early Detection of Cancer; Humans; Intubation, Gastrointestinal; Patient Compliance; Patient Education as Topic; Polyethylene Glycols; Randomized Controlled Trials as Topic | 2017 |
Dietary intake of vitamins A, C, and E and the risk of colorectal adenoma: a meta-analysis of observational studies.
To comprehensively summarize the association between dietary intake of vitamins A, C, and E and the risk of colorectal adenoma (CRA), the precursor of colorectal cancer, relevant studies were identified in MEDLINE and EMBASE up to 31 October 2012. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were pooled with a random-effects model. Between-study heterogeneity was assessed using Cochran's Q and I statistics. A total of 13 studies with 3832 CRA cases were included in this meta-analysis. On the basis of the highest versus lowest analysis, dietary intake of vitamin C reduced the risk of CRA by 22% (SRRs 0.78, 95% CIs: 0.62-0.98). Subgroup analyses showed that this relation was not modified by BMI, smoking status, and dietary energy intake. Further, dietary intake of β-carotene was also inversely associated with the risk of CRA. However, dietary intake of vitamins A and E was not associated with the risk of CRA in overall and subgroup analyses (vitamin A: SRRs 0.87, 95% CIs: 0.67-1.14; vitamin E: SRRs 0.87, 95% CIs: 0.69-1.10). Our results indicate that dietary intake of vitamin C and β-carotene, but not vitamins A and E, could reduce the risk of CRA. However, these associations seem to be limited. Further investigation using large samples and a rigorous methodology is warranted. Topics: Adenoma; Ascorbic Acid; Clinical Trials as Topic; Colorectal Neoplasms; Diet; Humans; Prognosis; Risk Factors; Vitamin A; Vitamin E | 2013 |
Antioxidants in the chemoprevention of colorectal cancer and colorectal adenomas in the general population: a systematic review and meta-analysis.
Antioxidants, such as vitamin A, C and E, selenium and β-carotene, have been proposed as possible agents in the chemoprevention of colorectal cancer and have been the subject of recent trials and reviews. This review aimed to assess the present evidence on the effect of antioxidants on the incidence of colorectal neoplasms in the general population.. A systematic review of randomized controlled trials was undertaken comparing antioxidants alone or in combination with other agents vs placebo. The following databases were searched for published and unpublished literature: Cochrane Library, MEDLINE, PreMEDLINE, CINAHL, EMBASE, Web of Science, and Biological Abstracts and Research Registers. Studies were quality appraised and extracted. Meta-analysis was performed.. Twelve studies were identified as relevant. In the nine comparing antioxidants with no antioxidants (n=148 922), there was no difference in the incidence of colorectal cancer [relative risk (RR) 1.00, 95% confidence interval (CI) 0.88-1.13]. One study assessed the effect of antioxidants on adenoma formation (n=15 538) and did not demonstrate a statistically significant effect (RR 1.47, 95% CI 0.97-2.23). Of 14 discrete analyses for different combinations of antioxidants, only one reported a statistically significant increase in relative risk of adenoma formation in participants receiving vitamin E (RR 1.74, 95% CI 1.09-1.79, P=0.02) or vitamin E plus β-carotene (RR 1.63, 95% CI 1.01-2.63, P=0.04). Effectiveness did not seem to differ between healthy populations, participants with cardiovascular risk factors or populations exposed to smoking or asbestos.. The review demonstrates that antioxidants (vitamin A, C and E, selenium and β-carotene), as single agents, in combination with other antioxidants or in combination with other agents, are not effective in the chemoprevention of colorectal neoplasia in the general population. This questions their involvement in future randomized controlled trials of chemoprevention in colorectal cancer. Topics: Adenoma; Antioxidants; Ascorbic Acid; beta Carotene; Colorectal Neoplasms; Humans; Selenium; Vitamin A; Vitamin E | 2011 |
Chemoprevention of colon cancer.
Animal tumor experiments and epidemiologic studies suggest that several agents may be of potential value in blocking the development of colon adenomas and carcinoma. Recent laboratory investigations have demonstrated several intermediate markers that are altered in the colonic epithelium of high-risk individuals and that can be modulated by several possible chemopreventive agents. Calcium and ascorbic acid are two agents that have been investigated in preliminary studies. Although the results have not been striking, these studies have pointed up methodologic issues that must be addressed and will contribute greatly to the design of the next generation of trials. Given the advances in the elucidation of the carcinogenic processes in colon cancer, it is reasonable to hope that the next decade of research will discover chemoprevention strategies that will protect individuals from the development of the most common tumor in Western society. Topics: Adenoma; Ascorbic Acid; Calcium; Colonic Neoplasms; Humans; Research Design | 1989 |
Blocking the formation of N-nitroso compounds with ascorbic acid in vitro and in vivo.
Topics: Adenoma; Amines; Aminopyrine; Animals; Ascorbic Acid; Dimethylnitrosamine; Female; Liver; Lung Neoplasms; Mice; Morpholines; Neoplasms, Experimental; Nitrites; Nitrosamines; Nitroso Compounds; Pregnancy; Rats; Urea | 1975 |
[Criteria of early morphological diagnosis of malignant epithelial proliferations of the thyroid].
Topics: Adenoma; Ascorbic Acid; Carcinoma; Cytodiagnosis; Glycogen; Glycosaminoglycans; Goiter, Nodular; Histocytochemistry; Humans; Hyperplasia; Karyometry; Precancerous Conditions; Thyroid Gland; Thyroid Neoplasms; Thyroiditis, Autoimmune | 1972 |
9 trial(s) available for ascorbic-acid and Adenoma
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Optimal Timing of Simethicone Addition for Bowel Preparation Using Polyethylene Glycol Plus Ascorbic Acid.
Colonic bubbles obscure the colonic mucosa during colonoscopy following bowel preparation with polyethylene glycol plus ascorbic acid (PEG-Asc). Simethicone is used to enhance visualization during colonoscopy. We aimed to determine the optimal timing of simethicone addition to improve bowel preparation using PEG-Asc.. This prospective, randomized study enrolled patients undergoing elective colonoscopy from April 2017 to January 2018. They were randomly assigned to one of the following three groups: PEG-Asc only (control) or simethicone addition in the morning on the day of colonoscopy (PEG-S1) or in the evening of the day prior to colonoscopy (PEG-S2). The primary outcome was the quality of colon cleansing, and the secondary outcomes were the adenoma detection rate (ADR), polyp detection rate (PDR), and diminutive (≤ 5 mm) ADR.. In total, 240 patients were randomly allocated to the three groups; six patients were withdrawn. Of the 234 patients evaluated, 78, 79, and 77 were allocated to the control, PEG-S1, and PEG-S2 groups, respectively. The bubble scores of all colonic segments were lowest in the PEG-S2 group. There was no significant difference in ADR or PDR among the three groups. However, the diminutive ADR was significantly higher in the PEG-S2 group compared to the other two groups (control 5.1% vs. PEG-S1 8.9% vs. PEG-S2 20.8%; P = 0.009).. Addition of simethicone to PEG-Asc at the optimal time prevents the formation of air bubbles and so improves the quality of bowel preparation, especially enhancing diminutive ADR. Topics: Adenoma; Adult; Aged; Antifoaming Agents; Ascorbic Acid; Cathartics; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Polyethylene Glycols; Prospective Studies; Simethicone | 2019 |
Efficacy and Acceptability of 1 Liter of Polyethylene Glycol with Ascorbic Acid vs. 2 Liters of Polyethylene Glycol Plus Mosapride and Sennoside for Colonoscopy Preparation.
BACKGROUND [color=black]Bowel preparation is an important factor for an optimal outcome of colonoscopy. Recently, polyethylene glycol (PEG) solution has been in common use for bowel cleansing for colonoscopy, but some patients are intolerant of PEG because of taste or volume. A low-volume PEG administered with ascorbic acid solution (PEG-Asc) was designed to improve tolerability, but the administration of this method is more complex than that with PEG alone. This study aimed to compare bowel cleansing efficacy, safety, and tolerability of 1 L PEG-Asc with a 2 L PEG preparation with use of sennosides and mosapride.[/color] MATERIAL AND METHODS [color=black]This was a prospective, single-center, non-inferiority trial that included 112 patients (PEG-Asc group, 68; PEG group, 44). The primary endpoint was the efficacy of colon cleansing assessed by endoscopists using a validated 4-point scale according to the Aronchick scale and was verified by a blinded investigator. Acceptability, tolerability, and adenoma detection rate (ADR) of these 2 regimens were secondary endpoints.[/color][color=black] [/color] RESULTS [color=black]We found no statistically significant differences between the groups in colon-cleansing efficacy or in the adenoma detection rate (ADR). Moreover, overall, patients significantly favored PEG-Asc over PEG, reflecting better acceptance of PEG-Asc. Additionally, more patients favored PEG-Asc over PEG for a hypothetical future colonoscopy. [/color] CONCLUSIONS [color=black]The alternate 1 L PEG-Asc regimen and standard 2 L PEG regimen were clinically equivalent with respect to cleansing efficacy, safety, and ADR, and more patients favored PEG-Asc than PEG. This alternate regimen may improve patient compliance and acceptance of surveillance colonoscopy.[/color]. Topics: Adenoma; Adult; Aged; Ascorbic Acid; Benzamides; Colitis, Ulcerative; Colonic Neoplasms; Colonoscopy; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Morpholines; Polyethylene Glycols; Senna Extract; Sennosides; Surveys and Questionnaires; Young Adult | 2018 |
Comparison of Two Intensive Bowel Cleansing Regimens in Patients With Previous Poor Bowel Preparation: A Randomized Controlled Study.
Inadequate bowel cleansing is a major burden for endoscopy units. The aim of this study was to compare two intensive bowel cleansing regimens in patients with previous colonoscopy with inadequate bowel preparation.. Patients with inadequate cleansing at index colonoscopy were randomized to 4-L split-dose polyethylene-glycol (PEG) regimen vs. 2-L split-dose PEG plus ascorbic acid (PEG+Asc) regimen. All individuals underwent a 3-day low-residue diet and received 10 mg of bisacodyl, the day before colonoscopy. Cleansing was considered to be adequate if the Boston Bowel Preparation Scale scored ≥2 at each colonic segment. A non-inferiority analysis was performed to demonstrate that colonic cleansing with 2-L PEG+Asc was not inferior to 4-l PEG, considering a non-inferiority margin of 10%.. Adequate bowel cleansing was significantly higher in patients assigned to 4-L PEG regimen (n=127) vs. those randomized to 2-L PEG+Asc regimen (n=129) by intention-to-treat analysis (81.1 vs. 67.4%, odds ratio (OR) 2.07, 95% confidence interval (CI) (1.163-3.689)) and by per-protocol analysis (86.6 vs. 71.7%, OR: 2.55, 95% CI: (1.316-4.922)). The study was terminated for futility after the interim analysis, because the 95% CI of the difference of proportions was 3.13-24.27% in the intention-to-treat analysis and 3.33-26.47% in the per-protocol analysis, confirming the superiority of 4-L PEG preparation.. After 3-day low-residue diet and oral bisacodyl before colonoscopy, colon cleansing with 4-L split-dose PEG was superior to 2-L split-dose PEG+Asc in patients with previous inadequate cleansing. (EUDRACT: 2013-002506-31, NCT02073552). Topics: Adenoma; Aged; Ascorbic Acid; Bisacodyl; Cathartics; Cecum; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Dietary Fiber; Early Termination of Clinical Trials; Female; Humans; Intention to Treat Analysis; Intubation, Gastrointestinal; Male; Middle Aged; Nausea; Polyethylene Glycols; Vitamins | 2017 |
A randomized controlled trial comparing a prepackaged low-residue diet with a restricted diet for colonoscopy preparation: the impact on the results of colonoscopy in adenoma detection.
This study aimed to investigate the clinical utility of a prepackaged low-residue diet (PLD) compared with a restricted diet (RD) for colonoscopic bowel preparation.. A prospective randomized controlled trial was carried out with patients undergoing colonoscopy. One hundred patients were randomly assigned to PLD and RD groups. In the RD group, the patients received an information sheet containing acceptable low-residue options and instructions from the medical staff. All patients received 10 ml sodium picosulphate the day before colonoscopy and 1 l of polyethylene glycol with ascorbic acid (PEG-A) on the day of the colonoscopy. If the bowel preparation was not adequate, an additional PEG-A solution was given. The primary outcome was the efficacy of colonic cleansing as rated by the Boston Bowel Preparation Scale (BBPS). The additional amount of PEG-A solution, adenoma detection rate and patient tolerance were assessed as secondary outcomes.. The BBPS score in the PLD group was 7.3 ± 1.7 compared with 6.5 ± 1.7 in the RD group. The quality of bowel preparation was significantly better in the PLD group (P < 0.05). The mean amount of additional PEG-A solution in the PLD group was smaller than in the RD group (293.8 ± 474.8 vs 444.1 ± 625.0 ml), but there was no statistical difference between the two groups. Adenoma detection rates and patient tolerance were similar in the two groups.. Prepackaged low-residue diets PLD is superior to RD for bowel preparation for colonoscopy. Topics: Adenoma; Aged; Ascorbic Acid; Cathartics; Citrates; Colonoscopy; Colorectal Neoplasms; Diet; Female; Humans; Male; Middle Aged; Organometallic Compounds; Picolines; Polyethylene Glycols; Preoperative Care | 2016 |
[Randomized controlled trial of sodium phosphate tablets versus 2 L polyethylene glycol solution for bowel cleansing prior to colonoscopy].
Performance of polyethylene glycol solution (PEG) is often unsatisfactory as bowel preparation agent for colonoscopy. In order to provide equivalent efficacy with better patient tolerance, sodium phosphate tablet (SPT) has been developed. This study was carried out to compare the efficacy and compliance of two bowel preparation methods: PEG with ascorbic acid (PEGA) vs. SPT preparation.. A multicenter, randomized controlled trial was performed. Primary efficacy variable was overall quality of colon cleansing assessed by Boston bowel preparation scale (BBPS) during colonoscopy. Patient's satisfaction and adverse events were evaluated by means of symptom questionnaire completed by each patient immediately before colonoscopy.. A total of 189 patients were randomly assigned to undergo pre-colonoscopic bowel preparation with either SPT (n = 96) or PEGA (n = 93). Overall BBPS score was 8.3 ± 1.12 in the SPT group and 8.4 ± 0.96 in the PEGA group (p = 0.441). Among the 189 patients, 90 had polyps (47.6%) and 50 had adenomas (26.5%). The polyp/adenoma detection rate was 54.2% (n = 52)/27.1% (n = 26) for SPT group and 40.9% (n = 38)/25.8% (n = 24) for PEGA group (p = 0.079 and 0.790, respectively). More number of patients were unable to take the prescribed dose of PEGA compared with the SPT regimen (8.6% vs. 2.0%, p = 0.045). Overall satisfaction score was 7.9 ± 1.63 in the SPT group and 7.4 ± 1.53 in the PEGA group (p = 0.022).. Degree of colon preparation, polyp/adenoma detection rate and adverse effect were similar between SPT group and PEGA group. Patient compliance and satisfaction were greater in the SPT group. Topics: Abdominal Pain; Adenoma; Adult; Ascorbic Acid; Cathartics; Colonic Polyps; Colonoscopy; Female; Humans; Male; Middle Aged; Nausea; Patient Satisfaction; Phosphates; Polyethylene Glycols; Surveys and Questionnaires | 2015 |
Efficacy of morning-only 4 liter sulfa free polyethylene glycol vs 2 liter polyethylene glycol with ascorbic acid for afternoon colonoscopy.
To compare the bowel cleansing efficacy of same day ingestion of 4-L sulfa-free polyethylene glycol (4-L SF-PEG) vs 2-L polyethylene glycol solution with ascorbic acid (2-L PEG + Asc) in patients undergoing afternoon colonoscopy.. 206 patients (mean age 56.7 years, 61% male) undergoing outpatient screening or surveillance colonoscopies were prospectively randomized to receive either 4-L SF-PEG (n = 104) or 2-L PEG + Asc solution (n = 102). Colonoscopies were performed by two blinded endoscopists. Bowel preparation was graded using the Ottawa scale. Each participant completed a satisfaction and side effect survey.. There was no difference in patient demographics amongst groups. 4-L SF-PEG resulted in better Ottawa scores compared to 2-L PEG + Asc, 4.2 vs 4.9 (P = 0.0186); left colon: 1.33 vs 1.57 respectively (P = 0.0224), right colon: 1.38 vs 1.63 respectively (P = 0.0097). No difference in Ottawa scores was found for the mid colon or amount of fluid. Patient satisfaction was similar for both arms but those assigned to 4-L SF-PEG reported less bloating: 23.1% vs 11.5% (P = 0.0235). Overall polyp detection, adenomatous polyp and advanced adenoma detection rates were similar between the two groups.. Morning only 4-L SF-PEG provided superior cleansing with less bloating as compared to 2-L PEG + Asc bowel preparation for afternoon colonoscopy. Thus, future studies evaluating efficacy of morning only preparation for afternoon colonoscopy should use 4-L SF-PEG as the standard comparator. Topics: Adenoma; Ascorbic Acid; Cathartics; Colonic Neoplasms; Colonic Polyps; Colonoscopy; Drug Administration Schedule; Female; Florida; Humans; Male; Middle Aged; Patient Satisfaction; Polyethylene Glycols; Predictive Value of Tests; Prospective Studies; Single-Blind Method; Surveys and Questionnaires; Therapeutic Irrigation; Time Factors | 2014 |
Antioxidant micronutrients and biomarkers of oxidative stress and inflammation in colorectal adenoma patients: results from a randomized, controlled clinical trial.
Previous epidemiologic observational and experimental studies investigated the potential of antioxidant micronutrients to modulate cancer risk, but these studies produced inconsistent results. In this pilot, randomized, double-blind, placebo-controlled clinical trial (n = 47), we assessed the effects of an antioxidant micronutrient combination (800 mg dl-alpha-tocopherol acetate, 24 mg beta-carotene, 1.0 g vitamin C, 200 microg l-selenomethionine, 7.2 mg riboflavin, 80 mg niacin, 60 mg zinc, 5 mg manganese) given daily over 4 months on oxidative and inflammatory biomarkers in patients with a history of sporadic colorectal adenoma. Plasma tumor necrosis factor-alpha (TNF-alpha), interleukin-6, and F2-isoprostane concentrations were measured using ELISAs, and cystine (CySS) was measured using high-performance liquid chromatography. Plasma TNF-alpha concentration decreased in the active treatment group by 37% relative to the placebo group (P = 0.002), and CySS decreased by 19% (P = 0.03); however, interleukin-6 and F2-isoprostane concentrations decreased in antioxidant-treated nonsmokers but increased in smokers, although these findings were not statistically significant. The decreases of TNF-alpha and CySS were more pronounced in nonsmokers. These data suggest that (a) an antioxidant micronutrient cocktail can modulate biomarkers of oxidative stress and inflammation in humans and (b) the effects of antioxidant micronutrient supplementation on biomarkers of inflammation and oxidative stress may differ according to smoking status. Topics: Adenoma; Adult; Aged; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers, Tumor; Chromatography, High Pressure Liquid; Colorectal Neoplasms; Cystine; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; F2-Isoprostanes; Female; Humans; Interleukin-6; Male; Manganese; Micronutrients; Middle Aged; Niacin; Oxidative Stress; Pilot Projects; Riboflavin; Selenomethionine; Tumor Necrosis Factor-alpha; Vitamin E; Zinc | 2010 |
Growth and recurrence of colorectal polyps: a double-blind 3-year intervention with calcium and antioxidants.
Dietary calcium and antioxidants have been suggested as protective agents against colorectal cancer. This has been supported by animal experimental studies, case control and cohort studies.. In a prospective intervention study of colorectal adenomas, and intermediary stage in colorectal carcinogenesis, 116 polyp-bearing patients received a placebo-controlled daily mixture of beta-carotene 15 mg, vitamin C 150 mg, vitamin E 75 mg, selenium 101 microg, and calcium (1.6 g daily) as carbonate for a period of 3 years with annual colonoscopic follow-up to test if the mixture was able to reduce polyp growth or recurrence. All polyps of < 10 mm at enrollment or follow-up were left unresected until the end of the study.. 87-91% of the patients attended the annual endoscopic follow-up investigations, and 19% of the patients dropped out of the medical intervention. The rest consumed 85% of the total amount of tablets over the 3 years. The fecal calcium concentration was 2.3-2.7 times higher in patients taking active medication compared to the placebo group. Diet registration showed that, when adding the intake of antioxidants and calcium from diet and intervention, there was a significant difference between the intake of these substances in the active and the placebo group. No difference was detected in the growth of adenomas between the active and the placebo group from year to year and for the total study period. Moreover, there was no effect on polyps of < 5 or 5-9 mm, or on polyps in the different colonic segments analyzed separately. A reduced growth of adenomas was found in patients <60 years of age taking active medication (n = 8) compared to those taking placebo (n = 6; mean difference 2.3 mm; 95% CI 0.26-4.36). There was a significantly lower number of patients free of new adenomas in the placebo group compared to those taking active medication as tested by logistic regression and Kaplan-Meier analysis (log-rank test p value 0.035). Subgroup analysis showed that only the group of patients with no family history of colorectal cancer, those with only one adenoma at inclusion, and those <65 years benefitted from the intervention medication.. The study did not find an overall effect on polyp growth. Our data, however, may support a protective role of calcium and antioxidants on new adenoma formation. Topics: Adenoma; Aged; Antioxidants; Ascorbic Acid; Calcium, Dietary; Cell Division; Colonic Polyps; Colorectal Neoplasms; Constipation; Diarrhea; Diet; Double-Blind Method; Dyspepsia; Energy Intake; Female; Follow-Up Studies; Gastrointestinal Diseases; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Patient Compliance; Patient Dropouts; Prospective Studies; Time Factors; Vitamin A | 1998 |
Effect of vitamin A, C, and E supplementation on rectal cell proliferation in patients with colorectal adenomas.
Studies suggest that cell proliferation abnormalities of the colorectal mucosa are associated with risk of neoplasia, and most cancers of the large bowel are thought to arise from adenomas. The results of other studies suggest that vitamins A, C, and E have chemopreventive efficacy against colon cancer in animal models. This study evaluates the effect of dietary vitamin supplementation on cell kinetics in uninvolved rectal mucosa in patients with colorectal adenomas. Twenty patients with colorectal adenomas were given vitamins A, C, and E for 6 months after complete polypectomy, and 21 patients with adenomas received placebo. In each patient, six biopsy specimens were taken from normal-appearing rectal mucosa before treatment and after 3 and 6 months of treatment and were incubated with tritiated thymidine ([3H]thymidine), and the [3H]thymidine-labeled cells were counted by use of autoradiography. Two parameters of cell proliferation were evaluated: 1) the ratio of the number of labeled cells to the total number of cells (thymidine labeling index) and 2) the ratio of the number of labeled cells in the upper 40% of the crypt to the total number of labeled cells in the crypt (phi h). The latter index reflects abnormal expansion of the proliferative compartment and is thought to be an intermediate biomarker of cancer risk. In patients receiving vitamins, phi h decreased progressively from baseline values, with increasing statistical significance (P less than .05 after 3 months, P less than .01 after 6 months). There was a statistically significant decrease in the thymidine labeling index in the 40% of the crypt near the mucosal surface, but the variation in the overall labeling index was not statistically significant. In the placebo group, we observed no statistically significant change in cell kinetics. These findings suggest that vitamin A, C, and E supplementation is effective in reducing abnormalities in cell kinetics that may indicate a precancerous condition. Before larger trials on chemoprevention of colorectal adenoma recurrence are conducted, additional studies are needed (a) to validate that cell kinetics is an intermediate biomarker, (b) to determine active agents, optimal dosage, and the relative efficacy of agents given alone and in combination, and (c) to test toxicity. Topics: Adenoma; Adult; Aged; Aged, 80 and over; Anticarcinogenic Agents; Ascorbic Acid; Cell Division; Colorectal Neoplasms; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Rectum; Vitamin A; Vitamin E; Vitamins | 1992 |
12 other study(ies) available for ascorbic-acid and Adenoma
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Efficacy of oral sulfate tablets for bowel preparation and adenoma detection rate.
The adenoma detection rate (ADR), which is closely related to bowel preparation, is the most important factor for colonoscopy quality assessment. New oral sulfate tablets (OSTs) have been developed to improve bowel preparation compliance. This study evaluated the efficacy of OSTs in terms of the ADR and bowel preparation status.. Medical records of subjects under the age of 65 who underwent colonoscopy from March 2019 to February 2021 were retrospectively reviewed. Polyethylene glycol with ascorbic acid (PEG-A) was used as a bowel preparation for the first half of the study period, and OSTs were used for the second half. In total, 16 971 subjects were included in the study: 9199 (54.2%) used PEG-A, and 7772 (45.8%) used OSTs. Bowel cleansing quality was assessed by the Boston Bowel Preparation Scale (BBPS).. The average age was 50 years. The rate of adequate bowel preparation was higher in the OST group than in the PEG-A group (97.2% vs 95.0%, P < 0.001). The mean BBPS was also higher in the OST group (8.02 vs 7.75, P < 0.001). The adenomas per colonoscopy (APC), the ADR and the sessile serrated polyp detection rate (SSPDR) were higher in the OST group than in the PEG-A group (APC 0.56 ± 1.01 vs 0.48 ± 0.91, P < 0.001; ADR 34.5% vs 30.7%, P < 0.001; SSPDR 5.2% vs 3.3%, P < 0.001).. Compared with PEG-A, OSTs yielded superior APC, ADRs, SSPDRs, and better bowel cleanliness. Therefore, OSTs are a good alternative for patients who have difficulty taking large-volume bowel preparation formulations. Topics: Adenoma; Ascorbic Acid; Cathartics; Colonoscopy; Humans; Middle Aged; Patient Satisfaction; Polyethylene Glycols; Retrospective Studies; Sulfates; Tablets | 2023 |
In vivo evidence of ascorbate involvement in the generation of epigenetic DNA modifications in leukocytes from patients with colorectal carcinoma, benign adenoma and inflammatory bowel disease.
A characteristic feature of malignant cells, such as colorectal cancer cells, is a profound decrease in the level of 5-hydroxymethylcytosine, a product of 5-methylcytosine oxidation by TET enzymes. Recent studies showed that ascorbate may upregulate the activity of TET enzymes in cultured cells and enhance formation of their products in genomic DNA.. The study included four groups of subjects: healthy controls (n = 79), patients with inflammatory bowel disease (IBD, n = 51), adenomatous polyps (n = 67) and colorectal cancer (n = 136). The list of analyzed parameters included (i) leukocyte levels of epigenetic DNA modifications and 8-oxo-7,8-dihydro-2'-deoxyguanosine, a marker of oxidatively modified DNA, determined by means of isotope-dilution automated online two-dimensional ultra-performance liquid chromatography with tandem mass spectrometry, (ii) expression of TET mRNA measured with RT-qPCR, and (iii) chromatographically-determined plasma concentrations of retinol, alpha-tocopherol and ascorbate.. Patients from all groups presented with significantly lower levels of 5-methylcytosine and 5-hydroxymethylcytosine in DNA than the controls. A similar tendency was also observed for 5-hydroxymethyluracil level. Patients with IBD showed the highest levels of 5-formylcytosine and 8-oxo-7,8-dihydro-2'-deoxyguanosine of all study subjects, and individuals with colorectal cancer presented with the lowest concentrations of ascorbate and retinol. A positive correlation was observed between plasma concentration of ascorbate and levels of two epigenetic modifications, 5-hydroxymethylcytosine and 5-hydroxymethyluracil in leukocyte DNA. Moreover, a significant difference was found in the levels of these modifications in patients whose plasma concentrations of ascorbate were below the lower and above the upper quartile for the control group.. These findings suggest that deficiency of ascorbate in the blood may be a marker of its shortage in other tissues, which in turn may correspond to deterioration of DNA methylation-demethylation. These observations may provide a rationale for further research on blood biomarkers of colorectal cancer development. Topics: Adenoma; Aged; alpha-Tocopherol; Ascorbic Acid; Case-Control Studies; Colorectal Neoplasms; DNA; Epigenesis, Genetic; Female; Humans; Inflammatory Bowel Diseases; Leukocytes; Male; Proto-Oncogene Proteins; RNA, Messenger; Vitamin A | 2018 |
Dietary factors and truncating APC mutations in sporadic colorectal adenomas.
Inactivating mutations in APC are thought to be early, initiating events in colorectal carcinogenesis. To gain insight into the relationship between diet and inactivating APC mutations, we evaluated associations between dietary factors and the occurrence of these mutations in a Dutch case-control study of sporadic colorectal adenomas (278 cases; 414 polyp-free controls). Direct-sequencing was used to screen adenomas for mutations in the mutation cluster region of APC; truncating mutations were detected in 161 (58%) of the adenomas. Red meat consumption was significantly differently related to polyps with truncating APC mutation (APC(+) polyps) compared to polyps without truncating APC mutation (APC(-) polyps) (highest vs. lowest tertile, odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.3-1.0). High intake of red meat and fat seemed to increase the risk of APC(-) polyps only (APC(+) vs. controls: red meat, OR = 1.0, 95% CI = 0.6-1.6; fat, OR = 1.1, 95% CI = 0.6-1.9; APC(-) vs. controls: red meat, OR = 1.8, 95% CI = 1.0-3.1; fat, OR = 1.9, 95% CI = 1.0-3.7). Intake of carbohydrates was inversely associated with both polyp groups, most noticeably with APC(-) polyps. Most other evaluated dietary factors were not distinctively associated with a specific APC status. None of the dietary factors was specifically associated with a particular type of truncating APC mutation. Our data suggest that red meat and fat may increase the risk of APC(-) polyps in particular, whereas carbohydrates may especially decrease the risk of APC(-) polyps. However, most examined dietary factors do not appear to be specifically associated with the occurrence of truncating APC mutations in colorectal adenomas but seem to affect both pathways equally. Topics: Adenoma; Adult; Aged; Alcohol Drinking; Animals; Ascorbic Acid; beta Carotene; Calcium, Dietary; Case-Control Studies; Colorectal Neoplasms; Dairy Products; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Dietary Proteins; DNA, Neoplasm; Edible Grain; Energy Intake; Feeding Behavior; Female; Fishes; Folic Acid; Fruit; Genes, APC; Humans; Male; Meat; Middle Aged; Mutation; Netherlands; Poultry; Sequence Analysis, DNA; Vegetables | 2005 |
Vitamin C intake and apoptosis in normal rectal epithelium.
Apoptosis, or programmed cell death, may lower the risk of neoplasia by removing genetically damaged or mutated cells. A high rate of apoptosis has been linked to a reduced risk of colorectal adenomas; therefore, it is important to understand factors that impact apoptosis. Antioxidants (e.g., vitamin C) protect cells from harmful oxidation processes but may interfere with apoptosis by protecting genetically damaged cells from reactive oxygen species-dependent cell death. The objective of this study was to evaluate the association between vitamin C intake and apoptosis in normal rectal mucosa. Study participants were part of a large, cross-sectional study, the Diet and Health Study III. Participants were recruited from consecutive, consenting patients who underwent colonoscopy at University of North Carolina Hospitals between August 1, 1998 and March 4, 2000. Vitamin C intake, obtained from a food frequency questionnaire, included both dietary sources and vitamin supplements. Apoptosis was measured by morphological evaluation of H&E-stained sections obtained from pinch biopsy samples of normal rectal mucosa in consenting participants (n = 503). The relationship between vitamin C and apoptosis varied by adenoma status. Among individuals with adenomas, there was an inverse linear association between apoptosis and total vitamin C intake. Similarly, individuals with adenomas in the highest quintile of total vitamin C intake were substantially less likely than those in the lowest quintile to have increased colonic apoptosis (odds ratio, 0.05; 95% confidence interval, 0.01-0.46). Vitamin C was not significantly associated with apoptosis in adenoma-free patients. High vitamin C intake was associated with reduced colorectal apoptosis among individuals with adenomas in this study population. Given that high apoptosis may lower colorectal cancer risk, vitamin C supplements may be contraindicated for patients with a history of adenomas. Topics: Adenoma; Adult; Antioxidants; Apoptosis; Ascorbic Acid; Colorectal Neoplasms; Cross-Sectional Studies; Eating; Energy Intake; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Multivariate Analysis; North Carolina; Rectum; Statistics as Topic; Treatment Outcome | 2003 |
Relation of serum antioxidant vitamins to the risk of colorectal adenoma.
The relation between risk of colorectal adenoma and serum concentrations of vitamins A, C, E and carotene was examined in a population-based case-control study of 105 cases of colorectal adenoma and a similar number of hospital controls showing no polyps at colonoscopy and a second control group of population controls. There were no significant associations with serum concentrations of vitamins C and E and carotene. Serum concentrations of vitamin A were significantly inversely related to the risk of colorectal adenoma when cases were compared with both control groups. After adjustment for energy intake, smoking, alcohol, estrogen therapy, body-mass-index and social class the inverse association between vitamin A and colorectal adenoma was even more marked. For the highest versus the lowest quartile of serum levels the adjusted RR was 0.23 (0.07-0.73) in relation to hospital controls and 0.08 (0.02-0.25) in relation to population controls. These findings suggest that the risk of developing colorectal adenomas is reduced in those with high vitamin A levels. Topics: Adenoma; Adult; Aged; Ascorbic Acid; Case-Control Studies; Colorectal Neoplasms; Female; Humans; Male; Middle Aged; Risk Factors; Vitamin A; Vitamin E | 2001 |
Dietary intake of specific carotenoids and vitamins A, C, and E, and prevalence of colorectal adenomas.
We determined whether intakes of the main dietary carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein plus zeaxanthin, and lycopene) and of vitamins A, C, and E were associated with the prevalence of colorectal adenomas among male and female members of a prepaid health plan in Los Angeles who underwent sigmoidoscopy (n = 488 matched pairs). Participants, ages 50-74 years, completed a 126-item semiquantitative food-frequency questionnaire and a non-dietary questionnaire from 1991 to 1993. In the univariate-matched analysis, alpha-carotene, beta-carotene (with and without supplements), beta-cryptoxanthin, lutein plus zeaxanthin, vitamin A (with and without supplements), and vitamin C (with and without supplements) were associated with a decreased prevalence of colorectal adenomas. After adjustment for intake of calories, saturated fat, folate, fiber, and alcohol, and for current smoking status, body mass index, race, physical activity, and use of nonsteroidal anti-inflammatory drugs, only beta-carotene including supplements was inversely associated with adenomas (odds ratio (OR), 0.6; 95% confidence interval (CI), 0.41.1; trend, P= 0.04; ORs compare highest to lowest quartiles0; vitamin C showed a weaker inverse association (OR, 0.8; 95% CI, 0.5-1.5; trend, P = 0.08); and the remaining compounds were no longer clearly associated with risk. After including beta-carotene with supplements and vitamin C simultaneously in the mutivariate model, the association of beta-carotene with supplements with adenomas was weakened (OR, 0.8; 95% CI, 0.5-1.3; trend P = 0.15), and vitamin C was no longer associated with risk. These data provide only modest support for a protective association of beta-carotene with colorectal adenomatous polyps. Topics: Adenoma; Aged; Anticarcinogenic Agents; Ascorbic Acid; beta Carotene; Carotenoids; Case-Control Studies; Colonic Neoplasms; Cryptoxanthins; Diet; Feeding Behavior; Female; Humans; Los Angeles; Lutein; Lycopene; Male; Middle Aged; Multivariate Analysis; Prevalence; Rectal Neoplasms; Risk Factors; Sigmoidoscopy; Vitamin A; Vitamin E; Xanthophylls; Zeaxanthins | 1996 |
Inhibitory effects of antioxidants on N-bis(2-hydroxypropyl)nitrosamine-induced lung carcinogenesis in rats.
Potential second-stage modifying effects of 8 antioxidants on lung tumorigenesis initiated by N-bis(2-hydroxypropyl)nitrosamine (DHPN) were examined in male F344 rats. After an initial 2-week treatment with DHPN (0.1% in drinking water), rats were administered one of the antioxidants supplemented in the diet for 30 weeks. Although the incidences of lung adenomas were not affected, those of carcinomas were lowered by 2% butylated hydroxyanisole (BHA, 2 rats/20 rats), 1% butylated hydroxytoluene (BHT, 1/20), 0.8% ethoxyquin (EQ, 3/20) and 1% a-tocopherol (a-TP, 2/20) treatments as compared to the control level (9/20), while 5% sodium L-ascorbate (SA), 0.8% catechol (CC), 0.8% resorcinol (RN), and 0.8% hydroquinone (HQ) did not exert any significant effect on incidence. Quantitative analysis of adenomas and carcinomas (numbers and areas of lesions per unit area of lung section) revealed obvious inhibitory effects of SA, CC, and RN as well as BHA, BHT, EQ, and a-TP. Among the antioxidants, BHT exerted the strongest inhibitory activity. In contrast, DHPN-induced thyroid tumorigenesis was significantly enhanced by BHT (14/20) and EQ (20/20) treatments (control = 5/20). Thus the antioxidants showed opposite effects on lung and thyroid carcinogenesis in the rat. Topics: Adenoma; Animals; Antioxidants; Ascorbic Acid; Body Weight; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Carcinoma; Catechols; Ethoxyquin; Hydroquinones; Kidney Neoplasms; Lung Neoplasms; Male; Nitrosamines; Organ Size; Rats; Rats, Inbred F344; Resorcinols; Thyroid Neoplasms; Urinary Bladder Neoplasms; Vitamin E | 1990 |
Modification by five antioxidants of 1,2-dimethylhydrazine-initiated colon carcinogenesis in F344 rats.
The effects of antioxidants given in the post initiation phase of colon tumor development were investigated in male F344 rats treated with 1,2-dimethylhydrazine (DMH). Animals (20/group) were given s.c. injections of DMH at a dose of 20 mg/kg once a week for four consecutive weeks. One week after the last injection, rats were fed diet containing 5% sodium L-ascorbate (SA), 0.5% butylated hydroxyanisole (BHA), 0.8% ethoxyquin (EQ), 1.0% propyl gallate or 0.5% butylated hydroxytoluene (BHT) for 36 weeks. A control group was fed the basal diet not containing antioxidants. The experiment was terminated 40 weeks after the first injection of DMH and all intestinal tumors were confirmed histologically. SA significantly increased the incidence of adenomas and the number of tumors per rat of the colon (especially of the distal colon). Although EQ and BHT did not affect the number of rats with colon tumors, the number of tumors per rat occurring in the distal colon was significantly increased by EQ while being decreased by BHT. No modification of tumor development was observed with BHA or PG. Thus, modification of tumor development by SA, EQ and BHT was apparent, mainly in the distal colon. Topics: 1,2-Dimethylhydrazine; Adenoma; Animals; Antioxidants; Ascorbic Acid; Butylated Hydroxyanisole; Butylated Hydroxytoluene; Carcinoma; Colonic Neoplasms; Dimethylhydrazines; Ethoxyquin; Male; Propyl Gallate; Rats; Rats, Inbred F344 | 1985 |
The effects of ascorbic acid and butylated hydroxyanisole in the chemoprevention of 1,2-dimethylhydrazine-induced large bowel neoplasms.
Human large bowel neoplasia seems to be caused by environmental carcinogens. The experimental carcinogen, 1,2-dimethylhydrazine (DMH), must be oxidized in the body to have effect. The antioxidants, butylated hydroxyanisole (BHA) and ascorbic acid, were tested for efficacy in prevention of experimental large bowel neoplasia. Carcinogenesis was induced in female CF-1 mice by administering DMH, 20 mg/kg, sq for 24 weekly doses. Test animals received varying doses of ascorbic acid, BHA, or both agents together. Animals were sacrificed when moribund or at 35 weeks. All colons were totally embedded and analyzed histologically. Ascorbic acid demonstrated no effects on incidence or density of large bowel tumors. Ascorbic acid did increase the ratio of adenomas to adenocarcinomas. BHA decreased the incidence and density of large bowel tumors. The lowest incidence was obtained in the group receiving both agents combined. It is concluded that BHA is effective in the chemoprevention of DMH-induced large bowel neoplasms. Ascorbic acid demonstrates only modest effect. The greatest effect on tumor incidence is seen when ascorbic acid and BHA are administered together. Topics: 1,2-Dimethylhydrazine; Adenocarcinoma; Adenoma; Administration, Oral; Animals; Anisoles; Ascorbic Acid; Butylated Hydroxyanisole; Colonic Neoplasms; Diet; Dimethylhydrazines; Female; Mice | 1984 |
Vitamin C and cancer.
Topics: Adenocarcinoma; Adenoma; Animals; Ascorbic Acid; Carcinogens; Humans; Neoplasms; Neoplasms, Experimental; Nitrosamines; Orthomolecular Therapy; Palliative Care; Rats | 1983 |
Surgical and medical measures in prevention of large bowel cancer.
Traditional methods for prevention of large bowel cancer rely on surveillance of patients with known precursors of bowel cancer, namely ulcerative colitis and those genetically linked polyposis syndromes that have malignant potential. Identification of heritable bowel cancer families and solitary polyp--cancer families provide additional populations that merit intensive scrutiny. Persuasive, if circumstantial, evidence suggests that maintaining patients free of large bowel polyps reduces the risk of developing large bowel cancer. Prospects for prevention of large bowel cancer are extended by recognition that a diet low in fat may reduce the risk of large bowel cancer. Furthermore, there is considerable evidence in animals that a variety of antioxidants limit large bowel carcinogenesis and preliminary evidence in man that these agents may control large bowel neoplasia. Topics: Adenoma; Ascorbic Acid; Colitis, Ulcerative; Colonic Neoplasms; Diet; Humans; Polyps; Precancerous Conditions | 1977 |
Induction of mouse lung adenomas by amines or ureas plus nitrite and by N-nitroso compounds: effect of ascorbate, gallic acid, thiocyanate, and caffeine.
Lung adenomas were induced in strain A mice by chronic treatment with N-nitroso compounds (given in drinking water) and with amines or ureas in food plus NaNO2 in drinking water. We studied the effects of varying the concentrations of three N-nitroso compounds and NaNO2 concentration in the morpholine plus NaNO2 and methylurea plus NaNO2 systems. Sodium ascorbate (NaASC) at the highest level tested (11.5 or 23 g/kg food) gave 89-98% inhibition of adenoma induction by the NaNO2 plus piperazine, morpholine, and methylurea systems. In 7 groups, NaASC produced increases of 15-59% in adenoma induction by nitrosomorpholine (NM) and mononitrosopiperazine (MNP), possibly because the mice consumed more of the nitrosamine solution. Adenoma induction by morpholine plus NaNO2 was strongly inhibited by gallic acid, moderately inhibited by caffeine, and unaffected by thiocyanate (all added to the food). Gallic acid inhibited or had no effect on the action of NM and MNP. We discussed the proposal that NaASC (or perhaps gallic acid) be administered with readily nitrosatable drugs. Topics: Adenoma; Amines; Animals; Ascorbic Acid; Caffeine; Dose-Response Relationship, Drug; Gallic Acid; Lung Neoplasms; Male; Methylurea Compounds; Mice; Mice, Inbred A; Morpholines; Neoplasms, Experimental; Nitrites; Nitroso Compounds; Piperazines; Thiocyanates; Urea | 1975 |