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

Using the dimethylbenz[a]anthracene-induced mammary tumor model, the present study demonstrated that a low vitamin E intake (7.5 mg/kg of diet) had minimal effect on carcinoma development in rats fed a 5% stripped corn oil diet, but resulted in a marked enhancement in tumor incidence and yield in those rats fed a 25% stripped corn oil ration. Control animals in this experiment received an adequate supply of vitamin E (30 mg/kg as DL-alpha-tocopheryl acetate). Thus, the effect of vitamin E deficiency on mammary carcinogenesis was accentuated in rats maintained on a high polyunsaturated fat diet, an observation similar to that of selenium deficiency which was reported by the author in a previous publication. In view of the biochemical interaction between vitamin E and selenium as endogenous antioxidants, another experiment was conducted to determine whether supranutritional supplementation of vitamin E (1000 mg/kg) was able to block the enhancement in mammary tumorigenesis due to selenium deprivation. Results of this experiment indicated that vitamin E excess failed to overcome the augmented tumor yield in selenium-deficient rats, nor did it provide any protection in rats that received an adequate supply of selenium. In summary, vitamin E deficiency may increase the risk of neoplastic development, especially when coupled with a high polyunsaturated fat intake; however, a high vitamin E supplementation does not seem to have any prophylactic effect on tumorigenesis by itself.
Carcinogenesis 1982
PMID:Dietary vitamin E intake and mammary carcinogenesis in rats. 681 42

Vitamins are a class of organic compounds that are components of an adequate diet. They or their derivatives function as coenzymes, cellular antioxidants, and/or regulators of gene expression. Fourteen vitamins are recognized in human nutrition (Vitamins A, D, E, K, B1, B2, B6, B12, C, niacin, folacin, pantothenic acid, biotin, choline), with deficiencies or excesses in intake leading to changes in protein, nucleic acid, carbohydrates, fat and/or mineral metabolism. Thus, the integrity of physiological systems, including those associated with detoxification, cellular repair, immune processes, and neural and endocrine function, depends upon the nutritional and vitamin status of the host. For these reasons, it may be anticipated that the adequacy of the vitamin supply to cells and tissues would affect the development, progress, and outcome of cancers. In this review, the definition and functions of and requirements and recommended allowance for vitamins are discussed briefly before exploring the evidence, largely from studies in experimental animals, that indicates the nature of the link between vitamins and cancer. Although evidence based on studies in animal systems reveals that vitamin intake and status can modulate the outcome of experimental carcinogenesis, the findings are often conflicting and difficult to interpret. Furthermore, it is not yet possible to develop a suitable prediction of the role of the individual vitamins in tumor development. The significance of these observations for human nutrition and cancer prevention, particularly in reference to ascorbic acid (vitamin C), vitamin E, and B-complex vitamins is considered. Vitamin A and retinoid compounds are discussed elsewhere in the symposium. The many popular misconceptions and unsound advice concerning vitamins and health, including "fake" vitamins-pangamic acid ("vitamin B15") and laetrile ("vitamin B17")-are also discussed. On the basis of current evidence, it would be inappropriate to recommend either substantial changes in habitual vitamin intakes, as provided by an adequate, well-balanced diet, or promotion of megavitamin intakes, as a means of reducing risk from cancers in the human population. However, a prudent approach toward diet and food habits, as a means of better optimizing the health consequences of our complex lifestyle is to be recommended.
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PMID:Vitamins and cancer prevention: issues and dilemmas. 723 79

This study investigates the effect of variations in dietary vitamin E on the incidence of dimethylhydrazine-induced colonic tumors in mice. Two groups of 65 LACA mice were given 28 weekly s.c. injections of dimethylhydrazine. The only difference in the management of the two groups was the dietary content of vitamin E; one group received 10 mg/kg, and the other group received 600 mg/kg. Of these two groups, 42 and 51 mice, respectively, survived, and there were significantly more adenomas, more adenomas with pleomorphic cytology, and more invasive carcinomas in the group receiving a low vitamin E supplement to their diet. It is suggested that vitamin E may have some part to play in the multifactorial effect of diet on colorectal carcinogenesis.
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PMID:Effect of dietary vitamin E on dimethylhydrazine-induced colonic tumors in mice. 735 60

I present evidence in support of a chemopreventive role for the so-called antioxidant nutrients, beta-carotene and vitamin E, against oral cavity cancer. This evidence is from laboratory studies, animal model systems, epidemiologic surveys, intervention trials involving reversal of premalignant changes, and prevention of malignancies in particularly high-risk subjects. Because agents proposed for disease prevention are meant to be used widely without close medical supervision, almost any toxicity is unacceptable. beta-Carotene and vitamin E fulfill this criterion for a suitable chemopreventive agent. In several epidemiologic studies, low intakes of vitamin E, carotenoids, or both have been associated with a higher cancer risk. Smoking, a major risk factor, results in lower beta-carotene concentrations in plasma and oral mucosal cells. In several laboratory and animal model systems, beta-carotene and other antioxidant nutrients are inhibitors of oral cavity carcinogenesis. beta-Carotene and vitamin E can produce clinical regression of oral leukoplakia, a premalignant lesion for oral cancer. The design and limitations of such studies in oral leukoplakia are discussed. Cancer incidence reduction trials in high-risk groups have targeted prevention of second malignancies in patients cured of a primary oral cancer. These trials are in progress. The data thus far are supportive of a significant preventive role for these nutrients in oral cancer.
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PMID:Antioxidants in oral cancer prevention. 749 39

The molecular mechanism of action of vitamin E on mammalian cells remains to be elucidated. In this study, vitamin E dietary intake was assessed for its effects on the initiation phase of carcinogenesis. We have conducted a dose-effect relationship between vitamin E dietary intake and aflatoxin B1 (AFB1) genotoxicity measured in vitro. Thus AFB1 induced mutagenesis in Salmonella typhimurium TA98 was investigated and compared to effect of vitamin E dietary intake on hepatic microsomal P-450 content and specific activities involved in AFB1 metabolism. Rats were fed ad libitum a diet containing 0, 0.05, 0.5 or 5 IU of alpha-tocopherol for 8 weeks. Modulation of vitamin E level in postmitochondrial and microsomal fractions resulted in nutritional effects. Cytochrome P-450 content was not modified by the level of vitamin E in the diet. The microsomal P-450 activities, P-450 IIB1 and IIIA, were decreased in the deficient group to -35% and -16%, respectively, as compared with control diet (0.05 IU). Diet supplemented with 0.5 IU of vitamin E increased P-450 IIB and IIIA activities (+28% and +37%, respectively) whereas a diet highly supplemented in vitamin E (5 IU) reduced these specific P-450 activities. Lipid peroxidation, estimated by the formation of thiobarbituric acid reactive products, increased in the dietary vitamin E free diet (+20%) and strongly decreased in the supplemented group (-99%). This study establishes that in vivo, dietary vitamin E protects directly membrane against damage induced by lipid peroxidation and indirectly hepatic microsomal monooxygenase activities. However, vitamin E accumulation seems to alter membrane structure and function. The nutritional effect of vitamin E on hepatic microsomal cytochrome P-450 activities modified the AFB1 genotoxicity measured in vitro.
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PMID:Effect of vitamin E dietary intake on in vitro activation of aflatoxin B1. 750 5

Because of the substantial morbidity and mortality associated with colorectal cancer, and the limitations and costs of treating this disease, prevention remains a desirable (if elusive) goal. In this paper, we discuss both chemo- and dietary prevention strategies for colorectal cancer, recognising the overlap and cross-fertilisation between these two approaches. Chemopreventive compounds are drugs and are developed for clinical use like other pharmaceuticals. A formal sequential multi-phase programme for development of chemopreventive agents has been instituted by the National Cancer Institute, U.S.A. This involves both preclinical efficacy and clinical studies. Such studies increasingly employ preneoplastic intermediate markers (such as proliferation measures) as well as neoplastic adenomas as endpoints. Promising chemopreventive agents include calcium, aspirin and other non-steroidal anti-inflammatory drugs, vitamins (such as vitamin E and folate), 2-dimethylfluorornithine (DFMO), oltipraz and ursodeoxycholic acid. Several lines of evidence implicate diet in colorectal carcinogenesis. Key hypotheses in diet and colorectal cancer (which are amenable to prevention, research and action), in addition to those pertaining to the micronutrient chemopreventives, include dietary fat and fibre, food mutagens, red meat, and overall low-fat, high-fibre, high fruit and vegetable dietary patterns and cuisines. Several adenomatous polyp recurrence studies with fibre supplement, macronutrient or dietary pattern interventions have been undertaken internationally. We review early findings from this new generation of studies, and anticipate the future results from these investigations and the ambitious Women's Health initiative in the U.S.A. Results from these studies may convert the promise of colorectal cancer prevention into reality.
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PMID:Chemo- and dietary prevention of colorectal cancer. 757 21

Several tumour promoting chemicals have been shown to inhibit intercellular communication (IC) through gap junctions in cell cultures. In the present investigation we studied the effect of the hepatic tumour promoters phenobarbital (PB), 1,1,1-trichloro-2,2-(p-chlorophenyl)ethane (DDT) and gamma-hexachlorocyclohexane (lindane) on IC in rat hepatocyte cultures. IC was evaluated by microinjection of fluorescent Lucifer Yellow CH dye and visualization of dye spread to adjacent hepatocytes. Incubation of hepatocytes with PB (2 mM), DDT (30 microM) and lindane (25 microM) decreased dye-coupling of the cells by about 30%, 42% and 35%, respectively; dye-coupling in untreated cultures was 88.1 +/- 0.7%. Inhibition of IC was reversible when the xenobiotics were removed from the medium. The antioxidant vitamin E (100 microM) prevented inhibition of dye-coupling by PB and lindane and partially that by DDT. Superoxide dismutase (100 units/microliters) counteracted the effect on dye-coupling by PB, but not that by the insecticides. Similarly, the cyclo-oxygenase inhibitors indomethacin and aspirin only reversed the effect of PB on IC, but not that of DDT or lindane. As indicated by further experiments, prevention by non-steroidal anti-inflammatory agents of PB-induced inhibition of IC is most likely not mediated by inhibition of cyclo-oxygenase. The results indicate significant differences in the action of PB, DDT and lindane on IC in hepatocyte cultures. This is suggested by the differential effects of superoxide dismutase and non-steroidal anti-inflammatory agents on the action of the three tumour promoting chemicals. Whereas superoxide radicals may be involved in the inhibition of dye-coupling by PB, radical intermediates of the insecticides may be responsible for the decrease in dye-coupling by DDT and lindane.
Carcinogenesis 1993 Nov
PMID:Inhibition of intercellular communication in rat hepatocytes by phenobarbital, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and gamma-hexachlorocyclohexane (lindane): modification by antioxidants and inhibitors of cyclo-oxygenase. 769 11

We have established an experimental model of oral contraceptive-induced hepatocellular carcinomas (HCCs) in female Wistar rats, revealing that ethynylestradiol (EE) and norethindrone acetate have actions as both initiators and promoters. The present time-sequence study was undertaken to clarify the role of free radicals in estrogen induction of HCC by measuring detoxifying enzyme activities and levels of 8-hydroxydeoxyguanosine (8-OH-dG) and by assessing the effects of concomitant vitamin C, vitamin E or beta-carotene administration on hepatocarcinogenesis. During 12 months oral administration of EE (0.075 or 0.75 mg/day), the 8-OH-dG levels reached peak values after 1 month, when they were significantly elevated as compared with the controls. Glutathione peroxidase demonstrated a tendency to decrease. Histologically, pre-neoplastic lesions assessed by immunohistochemical staining for placental glutathione S-transferase (GST-P) were first observed at 2 months in the groups given 0.075 and 0.75 mg/day of EE alone, with incidences of HCC at 12 months being 8.7% and 38.5% respectively. Combined administration of vitamins with 0.075 mg EE/day reduced the elevation of the 8-OH-dG levels. GST-P-positive lesions were first observed at 4 months in the vitamin E group and at 6 months in the vitamin C and beta-carotene groups. As compared with the value in the 0.075 mg EE alone group, vitamin administration significantly reduced the numbers of GST-P-positive foci after 12 months of treatment. The incidences of HCC at 12 months were 0% in the vitamin C group, 4.5% in the vitamin E group and 4.8% in the beta-carotene group, i.e. administration of the vitamins inhibited the development of GST-P-positive foci, with suppression of HCC. The results thus suggest that free radicals play an important role in the induction of HCC by estrogen.
Carcinogenesis 1995 Apr
PMID:Role of reactive oxygen in synthetic estrogen induction of hepatocellular carcinomas in rats and preventive effect of vitamins. 772 63

There is a considerable variation in the diets used in studies on the influence of dietary fat on rat mammary cancer. In view of the fact that diet is the most remarkable factor in these studies, the aim of this work was to define two experimental diets, one of them normal (N3) and another hyperlipidic (HL20), both allowing the normal growth of the rat and neither of them containing factors that could unspecifically affect mammary carcinogenesis. Semisynthetic diets were selected instead of natural ones. A normal diet (3% corn oil, 18% casein, 67.9% dextrose) and a hyperlipidic diet (20% corn oil, 23% casein, 45.9% dextrose) were defined for the rat. Both diets also contain 5% cellulose, 5.9% salt mix and 0.24% vitamin mix. In order to avoid the influence of the above mentioned unspecific factors, the control of specificity and quality of nutrients is proposed as an essential measure. Moreover, it is also necessary to adopt measures to avoid the presence of fatty acid metabolites, including the calculation of the necessary vitamin E, selenium and sulfur amino acid and the determination of factors potentially able to stimulate or inhibit carcinogenesis such as phenolic antioxidants, retinoids or the trans isomer of fatty acids. On the other had, casein, dextrose, choline and folic acid contents were modified in order to equilibrate the lipid increase experimentally introduced in the HL20 diet or to ensure the normal maintenance of the animals' metabolism. The method used is based on the concept of quality assurance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experimental diets for the study of lipid influence on the induced mammary carcinoma in rats: I--Diet definition. 777 45

The authors subdued 183 vegetarians to examination, the aim of which was to judge the state of health and nutrition of the vegetarian population. The examined group was composed of people with their age ranging from 19-60 years, out of which 102 were of younger (19-39 years) and 81 were of older age. Their average period of vegetarian food consumption was 4.2 years. One third of men and a half of women were lacto-vegetarians, the rest were lacto-ovo-vegetarians. The results were compared with 160 nonvegetarians (64 of younger and 96 of older age). The detected values of lipid parameters were evaluated as favourable for vegetarians (low values of cholesterol, triacylglycerols, atherogenic index, LDL-cholesterol, the share of HDL-cholesterol was 28-33% (vs 24-26% in nonvegetarians) with values converging to 1.4 mmol.l-1--i.e. reduced risk). Additional favourable factors in prevention of atherosclerosis include the absence of obesity in vegetarians and values of antisclerotic active substances in blood (high values of vitamin C, in comparison with nonvegetarians a significantly higher molar ratio of vitamin E/cholesterol and vitamin E/triacylglycerols--more effective protection against peroxidation of lipids). Vegetarian mode of food consumption may be favourably evaluated regarding prooxidative-antioxidative parameters which play an important role in the process of atherogenesis, and carcinogenesis. Significantly lower values of conjugated dienes in plasma of vegetarians and vice versa high values of antioxidant substances (vitamin C, vitamin E/lipid components, catalase activity) were detected. A more pronounced system of detoxication in vegetarians is important due to a possible risk of an increased intake of xenogenous substances. (Tab. 3, Ref. 27.)
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PMID:[Lipid and pro-oxidative and antioxidative parameters in the blood of vegetarians]. 855 57


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