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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies were made on the carcinogenic activity of butylated hydroxyanisole (BHA) in rats, mice, and hamsters and the effect of the antioxidants BHA, butylated hydroxytoluene (BHT), ethoxyquin (EQ), sodium L-ascorbate (SA), ascorbic acid (AA), sodium erythorbate (SE), propyl gallate (PG), and alpha-tocopherol, on two-stage chemical carcinogenesis in rats initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 1,2-dimethylhydrazine (DMH), diethylnitrosamine (DEN), 7,12-dimethylbenz(a)anthracene (DMBA), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), N-ethyl-N-hydroxyethylnitrosamine (EHEN), or N-methylnitrosourea (MNU). BHA clearly induced squamous cell carcinomas in both the rat and hamster forestomach. The tumorigenic action of crude BHA on the forestomach is largely due to 3-tert-BHA. In two-stage chemical carcinogenesis, BHA promoted MNNG or MNU-initiated forestomach and BBN- or MNU-initiated urinary bladder carcinogenesis and inhibited DEN- or EHEN-initiated liver and DMBA-initiated mammary carcinogenesis. BHT demonstrated promotion potential for urinary bladder and MNU-initiated thyroid carcinogenesis and inhibited DMBA-initiated ear duct carcinogenesis. EQ promoted EHEN-initiated kidney carcinogenesis and inhibited DMBA-initiated mammary and EHEN-initiated liver carcinogenesis. SA promoted forestomach and urinary bladder carcinogenesis and SE likewise enhanced urinary bladder carcinogenesis. alpha-Tocopherol inhibited ear duct carcinogenesis. No effects of any of the antioxidants on glandular stomach carcinogenesis were found. The results clearly demonstrated that antioxidants have different effects (promoting or inhibitory influences) depending on the organ studied and suggest the importance of a whole body approach to their investigation.
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PMID:Modifying effects of antioxidants on chemical carcinogenesis. 378 13

Studies were conducted on the carcinogenic activity of butylated hydroxyanisole (BHA) in rats and hamsters. To obtain information concerning the mechanism of action of BHA on the forestomach, the following areas were examined: the effects of 12 phenolic compounds structurally related to BHA on the hamster forestomach, the effects of combinations of BHA and other antioxidants on the rat forestomach, and the metabolism of BHA in the forestomach. Also examined were the effects of several antioxidants on two-stage carcinogenesis in rats. Squamous-cell carcinomas were induced in the forestomach of rats and hamsters fed BHA. In a limited study, 1 of 13 hamsters developed a squamous-cell carcinoma. The tumorigenic action of crude BHA on the forestomach was largely due to the action of 3-tert-BHA. p-tert-Butylphenol and 2-tert-butyl-4-methylphenol induced pronounced hyperplasia and papillomas in the hamster forestomach. BHA and other antioxidants, particularly propyl gallate and ethoxyquin, showed additive effects in inducing forestomach hyperplasia and cytotoxicity. Neither BHA nor its metabolites were found in the forestomach epithelium, although small amounts of metabolites were detected in the stomach contents. Thus, a direct action on the stomach epithelium may be exerted by BHA itself or by metabolites formed on interaction of BHA with gastric juice. BHA enhanced forestomach carcinogenesis initiated in rats by N-methyl-N'-nitro-N-nitrosoguanidine or N-methylnitrosourea (MNU) and enhanced urinary bladder carcinogenesis initiated by MNU or N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). In contrast, it inhibited carcinogenesis initiated in the liver by either diethylnitrosamine or N-ethyl-N-hydroxyethylnitrosamine (EHEN) and mammary carcinogenesis initiated by 7,12-dimethylbenz[a]anthracene (DMBA). BHT promoted urinary bladder carcinogenesis initiated by BBN or MNU and thyroid carcinogenesis initiated by MNU, but inhibited ear-duct carcinogenesis initiated by DMBA. Ethoxyquin promoted EHEN-initiated kidney carcinogenesis, but inhibited both DMBA-initiated mammary and EHEN-initiated liver carcinogenesis. Sodium ascorbate promoted forestomach and urinary bladder carcinogenesis, and sodium erythorbate also enhanced urinary bladder carcinogenesis. alpha-Tocopherol inhibited ear-duct carcinogenesis. No antioxidants tested had any effect on glandular stomach carcinogenesis. Thus antioxidants have independent modifying (promoting or inhibitory) effects in different organs.
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PMID:Studies on antioxidants: their carcinogenic and modifying effects on chemical carcinogenesis. 380 12

As a result of many studies in descriptive and analytic epidemiology, in animal carcinogenesis, and in the direct examination of body fluids for mutagens/carcinogens, it is possible to develop a list of dietary factors that may be associated with the high rate of colon cancer and related cancers in Western countries. This paper is concerned with the design of intervention studies to clarify which of these factors is important. The size of such intervention trials is influenced primarily by two factors: the incidence of the disease outcome studied in a control population and the magnitude of risk reduction in a treated group. Calculations based on a variety of assumptions suggest that a randomized trial in which cancer mortality is measured as the outcome of the intervention in a healthy population is probably too costly to be justified by current evidence linking the disease to diet. However, precursor lesions can be considered as an alternative outcome. The choice of the precursor lesion depends on the link to the disease in question, the prevalence of the lesion in the population, and the ease of detection. Recent developments in the application of endoscopic methods and in the description of the pathologic process leading to cancer suggest the use of gastrointestinal polyps as "precursor lesions" as the outcome of a trial. We illustrate these points with a protocol for a study in progress, a randomized double-blind study of the effect of ascorbic acid and alpha-Tocopherol on the rate of recurrence of colorectal polyps.
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PMID:Strategies for dietary intervention studies in colon cancer. 626 43

In the Basel study (BS) (1960-73) on cardiovascular and peripheral arterial diseases, a mortality follow-up was completed for the period 1965-80. Of the 4,224 men at risk for these diseases, 531 died. The causes of death were established from the death certificates and classified into 8 groups. For each case 2 age- and sex-matched controls were selected and compared with the corresponding cases with regard to the various variables obtained at the three examinations (1960, 1965, 1971). This report dealth with cancer mortality, plasma lipids, plasma vitamins, alcohol and cigarette consumption, and intake of milk and citrus fruits. The results were all obtained at the second follow-up examination (BS III, 1971-73). Cancer of the lung, stomach, large bowel, and all other sites were treated separately. The average follow-up from BS III until death varied from 3.7 years (other sites) to 4.9 years (cancer of the lung). Of 129 cancer deaths, the highest incidence was found for cancer of the lung (38) followed by stomach (19) and large bowel, (15) and the remainder (57) was for other sites. Plasma lipids did not differ significantly among cases and controls. However, the lowest values were observed in colorectal cancer and gastric carcinoma (mean cholesterol, 213 mg/dl). beta-Carotene was significantly lower in cancer cases of the lung than in controls (14.8 micrograms/dl vs. 23.7; P less than .05). It was also low in gastric cancer cases (13.0 micrograms/dl). Vitamin A was below average only in cases with gastric cancer (difference due to the small number not significant). Vitamin C was consistently lower in cancer cases than in controls. The lowest value was found for cancer of the stomach and corresponded to a below-average consumption of citrus fruits. Vitamin E was low in cancer of the colon. Plasma lipids correlated strongly with vitamin E (tau = 0.5) and to a lesser extent with vitamin A (tau = 0.25). beta-Carotene correlated poorly with beta-lipoproteins (low-density and very low-density lipoproteins) but significantly with total cholesterol. Smoking was inversely related, as was alcohol consumption, to the beta-carotene level. From these results, the conclusion was that vitamins influence carcinogenesis in humans.
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PMID:Cancer, vitamins, and plasma lipids: prospective Basel study. 659 56

Lead chromate induces chromosomal damage as a result of extracellular dissolution producing solubilized chromium and lead and we show here that the dissolution process is greatly accelerated by the presence of cells. We have sought to determine which of these ions is involved in lead chromate-induced clastogenicity. Cell-mediated extracellular dissolution of particulate lead chromate resulted in the accumulation of both solubilized chromium and solubilized lead, reaching concentrations in the extracellular medium of 15 and 1.9 microM respectively and reaching concentrations inside the cell of 2700 and 97 microM respectively. Both the extracellular and intracellular accumulation of chromium was time dependent and both the solubilized lead and chromium increased proportionately from a lower dose to a higher dose. Exposing cells to water soluble sodium chromate under conditions which produced similar time-dependent intracellular concentrations of chromium also produced a similar amount and spectrum of chromosome damage as lead chromate. In contrast, exposure to lead glutamate resulted in intracellular lead levels 438-times higher than those produced by lead chromate, but produced no chromosome damage. A higher dose of lead glutamate was weakly clastogenic, but it induced a different spectrum of chromosomal aberrations than lead chromate. Pretreatment of cells with vitamin E had no effect on the uptake of chromium, but reduced both sodium chromate- and lead chromate-induced clastogenesis by 54-93%. Vitamin E pretreatment did not affect lead glutamate-induced clastogenesis. The results of this study indicate that although lead(II) is weakly clastogenic at high doses, hexavalent chromium is the proximate clastogen in lead chromate-induced clastogenesis. Additionally, this is the first report that pretreatment of cells with vitamin E can block clastogenesis induced by particulate chromates.
Carcinogenesis 1994 Oct
PMID:Cell-enhanced dissolution of carcinogenic lead chromate particles: the role of individual dissolution products in clastogenesis. 795 62

The dorsal skins of 6-8 week old female SENCAR mice were initiated with a single application of 10 nmol of 7,12-dimethylbenz[a]anthracene (DMBA) and subsequently promoted twice/week with topical applications of vitamin E (dl-alpha-tocopherol, 80 mumol/treatment). Vitamin E from two separate commercial suppliers was tested. For comparison, a group of similar mice, also initiated with DMBA, was promoted twice/week with the known tumor promoter 12-O-tetradecanoylphorbol-13- acetate (TPA, 2 micrograms/treatment). Papillomas appeared 39 and 50 days respectively after promotion began with vitamin E from the two different sources, as compared with 32 days in the group receiving TPA promoted. Hundred per cent of TPA-promoted animals and 92-96% of the vitamin E-promoted mice developed tumors. A maximum of 15 papillomas/animal appeared in the TPA-promoted mice. The two vitamin E preparations were somewhat less effective than TPA and showed different relative potencies, producing about seven and 12 papillomas per animal respectively. Unlike TPA, vitamin E showed very little ability to produce an inflammatory response in skin. To test whether initiated cells that did not appear as papillomas after vitamin E promotion were still viable, and had proceeded past stage I of promotion (conversion), the group that developed 12 papillomas/animal from vitamin E promotion was further promoted with mezerein, a stage II promoter. In this group, the papilloma frequency then increased to approximately 17/animal. The animals were followed over the course of their lifespan and monitored for skin carcinomas. In the TPA-promoted group 64% of the mice developed carcinomas, while the two vitamin E-promoted groups showed 48 and 60% incidence respectively. These results indicate that topically applied vitamin E acts as a complete tumor promoter in DMBA-initiated mouse skin, with an efficiency approaching that of TPA. Since vitamin E is a powerful antioxidant, they also suggest that reduction of cellular oxidant levels may trigger the tumor promotional process, and it may therefore be prudent to avoid repetitive or prolonged topical exposure of human skin to antioxidants like vitamin E.
Carcinogenesis 1993 Apr
PMID:Vitamin E is a complete tumor promoter in mouse skin. 847 30

To a great extent carcinogenesis depends on the environment. Some vitamins contribute to the "exogenous" protection against aggressors (i.e., on a molecular scale, active forms of oxygen and free radicals). Epidemiology provides numerous data in favour of this protection, but these date are sometimes ambiguous or contradictory. Current, active experimental studies will probably lead to firm conclusions within the next few years. As regards vitamin A, considerable advances have been made in fundamental research (we now know its molecular mechanism of action, notably on genes) and in applied research (differentiation of leukaemic cells). In various aspects vitamin D resembles vitamin A and also acts on the haematopoietic tissue. Vitamin E is difficult to study, but its protective effect on cell membranes and structures cannot be questioned. Vitamin C emerges from a period of controversy and is increasingly studied at present: it might be a useful adjuvant for the treatment of cancers.
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PMID:[Vitamins and cancers]. 850 31

Although previous epidemiological studies have indicated that beta-carotene is an important agent for the chemical prevention against carcinogenesis, a recent prospective study has strikingly suggested that supplementation with beta-carotene significantly increased the incidence of some types of cancer (The alpha-Tocopherol and beta-Carotene Cancer Prevention Study Group, New Engl. J. Med., 330 (1994) 1031-1035). To analyze the discrepancy of this problem, the authors analyze the effects of beta-carotene on biochemical and biological events associated with carcinogenesis by in vitro experiments. (1) All-trans beta-carotene enhanced the proliferation and DNA synthesis of BALB/c 3T3 cells induced by a tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and fetal bovine serum, although beta-carotene itself did not show mitogenic activity. (2) All-trans beta-carotene caused a remarkable stimulation for the early induction of ornithine decarboxylase (ODC) activity after the stimulation of TPA and fetal bovine serum. (3) All-trans beta-carotene exhibited significant antimutagenic activity which suppresses umu C gene expression in Salmonella typhimurium (TA 1535/pSK 1002) induced by a typical mutagen, 2-aminoanthracene (2-AA). These experimental results suggest that all-trans beta-carotene might cause beneficial and harmful effects on different phases of carcinogenesis.
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PMID:All-trans beta-carotene enhances mitogenic responses and ornithine decarboxylase activity of BALB/c 3T3 fibroblast cells induced by tumor promoter and fetal bovine serum but suppresses mutagen-dependent umu C gene expression in Salmonella typhimurium (TA 1535/pSK 1002). 856 24

A placebo-controlled double-blind intervention trial was performed using 60 male volunteers aged between 50 and 70 years to test the hypothesis that intake of d-alpha-tocopherol (VITE) above the recommended dietary intake (RDI) level (10.0 mg or 14.9 IU VITE) can protect against DNA damage in human peripheral blood lymphocytes. The intervention consisted of two phases, each of 8 weeks duration: during the initial phase the VITE supplement was 5 x RDI (provided in cereal) and during the second phase the VITE supplement was 30 x RDI (provided in capsules). Blood samples were collected before the initial phase, between phases and at the end of the second phase; the level of VITE was measured in plasma using HPLC and genetic damage rate in peripheral blood lymphocytes was measured using the cytokinesis-block micronucleus assay. The study has shown that cereal supplementation is an effective route for an above RDI intake of VITE; a 5 x RDI supplement resulted in a 22% elevation in the plasma VITE status. By comparison the use of 30 x RDI supplementation with capsules as the route of delivery resulted in an 89% increment in plasma VITE status. The increased VITE status during the intervention, however, had no significant impact on the spontaneous genetic damage rate in human lymphocytes. There was also no correlation between baseline genetic damage frequency and VITE status. However, a 32% (P < 0.007) decrease in the micronucleus index was recorded in both the control and VITE-supplemented groups during the course of the study which could have been due either to seasonal effects or other common components in the diet such as the carrier used for the VITE in the cereal and the capsules. The study has identified a small proportion (3.4%) of apparently healthy individuals who are abnormally sensitive to oxidative stress by hydrogen peroxide and demonstrated that VITE supplementation did not attenuate the impact of the oxidative challenge on genetic damage rate. The above data suggest that supplements in cereal are a viable route for delivering VITE and that supplementation with VITE is unlikely to affect chromosome damage occurring spontaneously or as a result of exposure to oxidative radicals.
Carcinogenesis 1997 Feb
PMID:Vitamin-E supplements and their effect on vitamin-E status in blood and genetic damage rate in peripheral blood lymphocytes. 905 29

The aim of this study is to report the antimutagenic effect of vitamin A and vitamin E towards methylazoxymethanol (MAM)-induced mutagenesis in Salmonella typhimurium strain TA100 sensitive to alkylating agents. In order to characterize different levels of action of these two fat-soluble vitamins towards the mutagenicity of MAM, several assays have been considered to show the antimutagenic effect and the possible interactions of vitamins with MAM or with the bacteria. Thus, for each vitamin, three different assays with three different incubations have been conducted: (i) MAM, bacteria and vitamins together, (ii) MAM and vitamins, (iii) bacteria and vitamins. The results showed that both vitamins A and E present an antimutagenic effect towards MAM induced mutagenesis. alpha-Tocopherol seems to have an action directly on to the mutagenic agent, whereas the action of retinol is likely due to a protection of the bacterial genoma against MAM. These in vitro results could help to interpret results of colon carcinogenesis studies using animals induced by 1,2-dimethylhydrazine and fed vitamins supplemented diet.
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PMID:Effects of vitamins A and E on methylazoxymethanol-induced mutagenesis in Salmonella typhimurium strain TA100. 924 19


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