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

Aflatoxin B1 (AFB1) is a potent hepatotoxic and hepatocarcinogenic mycotoxin. The mechanism of cellular damages caused by AFB1 has not been fully elucidated. Lipid peroxidation is one of the main manifestations of oxidative damage and has been found to play an important role in the toxicity and carcinogenesis of many carcinogens. In this study, we investigated the induction of lipid peroxidation by AFB1 in the liver of Fischer 344 rats. Malonaldehyde (MDA) and conjugated dienes, both products of lipid peroxidation, were determined in liver homogenate and subcellular fractions. An increase of MDA and conjugated dienes in liver homogenate was detected 1 day after AFB1 administration. It reached the peak level 3 days after dosing and remained at an elevated level up to 14 days. The induction of MDA by AFB1 was also found to be dose-dependent. Measurements of lipid peroxidation in the subcellular fractions revealed that microsomes had the highest concentration of MDA, followed by those of the nuclear fraction and mitochondria. MDA concentration was not detectable in the cytosolic fraction. Further, it was found that pretreatment with selenium and vitamin E, both antioxidants, and deferoxamine, a specific iron chelator, significantly inhibited lipid peroxidation as well as liver cell damage. These results provide in vivo evidence that AFB1 can cause lipid peroxidation in rat liver. Oxidative damages caused by AFB1 may be one of the underlining mechanisms for AFB1-induced cell injury and DNA damage, which eventually lead to tumorigenesis.
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PMID:Aflatoxin B1-induced lipid peroxidation in rat liver. 804 46

Head and neck cancer remains a common cause of mortality and morbidity in the United States and throughout the world. In spite of advances in the management of patients with advanced disease, overall survival in this group remains poor. Furthermore, although cancer mortality is lower in patients with early-stage disease, treatment results in significant morbidity, and these patients also face the risk of developing a second primary tumor. Chemoprevention is an innovative approach to decrease overall cancer morbidity and mortality using substances that are capable of preventing cancer progression. Head and neck cancer is an excellent model for chemoprevention, as its biology is consistent with the two concepts important for the development of chemoprevention strategies: field cancerization and multistep carcinogenesis. Several classes of compounds have been evaluated in chemoprevention trials. The most frequently studied agents, the retinoids, were found frequently to induce remissions in patients with oral leukoplakia. Furthermore, retinoids prevented progression to malignancy in one randomized maintenance study. Other agents, including beta-carotene and vitamin E, have been found also to have activity in the management of oral leukoplakia. However, the clinical role of chemopreventive agents in reducing cancer mortality remains to be defined. Two studies, one in head and neck cancer and one in lung cancer, have shown the ability of retinoids to prevent the development of second primary tumors. Current large randomized trials are defining the effectiveness of these agents in reducing the mortality of aerodigestive tract tumors in individuals at high risk.
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PMID:Biology and chemoprevention of head and neck cancer. 805 3

High performance liquid chromatography with electrochemical detection (HPLC-EC) was used to measure 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker for oxidative DNA damage, in mammary gland isolated from tumor-bearing and tumor-free rats fed diets of varied fatty acid composition and vitamin E and selenium content. A method for tissue preparation and analysis is reported and a significant positive correlation shown between degree of unsaturation of dietary fatty acids and 8-OHdG concentration, regardless of antioxidant status. The increase in 8-OHdG concentration with greater fatty acid unsaturation was more pronounced in the absence of adequate dietary vitamin E and selenium. The implications of these data for defining the role of dietary lipid in the process of mammary carcinogenesis are discussed.
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PMID:Antioxidant status and dietary lipid unsaturation modulate oxidative DNA damage. 829 86

The ultimate proof that a putative chemopreventive agent does prevent cancer is a demonstration of reduced cancer incidence in a targeted population. However, because of practical and logistical considerations, such trials are virtually impossible to conduct for the majority of cancers. Therefore, a conclusion regarding the efficacy of chemopreventive activity is based on consideration of a variety of indirect lines of evidence, including laboratory studies, animal model systems, epidemiologic surveys, intervention trials involving reversal of premalignant changes, and the prevention of malignancies in particularly high risk subjects. Furthermore, the only agents worth testing are those with limited, or preferably, no toxicity, since the final use will be prevention in a generally healthy population. Beta-carotene and vitamin E both fulfill all the criteria for suitable chemopreventive agents; several lines of evidence point toward preventive roles for them in oral cancer. In numerous epidemiologic studies, low intake of beta-carotene has been associated with higher cancer risk. Both intake and supplemental use of vitamin E have been associated with a lowered risk of cancer. Smokers, whose habit is a major risk factor, have lower beta-carotene levels in oral mucosal cells when compared with non-smokers. In several laboratory and animal model systems, including the very relevant hamster cheek pouch model, these agents strongly inhibit oral cavity carcinogenesis. Beta-carotene and vitamin E produce regression of oral leukoplakia, a premalignant lesion for oral cancer. This has now been shown in seven clinical trials: five with beta-carotene alone, one with vitamin E, and one with a combination of both.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-carotene and vitamin E in oral cancer prevention. 841 3

Flavonoids are strong antioxidants that occur naturally in foods and can inhibit carcinogenesis in rodents. Accurate data on population-wide intakes of flavonoids are not available. Here, using data of the Dutch National Food Consumption Survey 1987-1988, we report the intake of the potentially anticarcinogenic flavonoids quercetin, kaempferol, myricetin, apigenin, and luteolin among 4,112 adults. The flavonoid content of vegetables, fruits, and beverages was determined by high-performance liquid chromatography. In all subjects, average intake of all flavonoids combined was 23 mg/day. The most important flavonoid was the flavonol quercetin (mean intake 16 mg/day). The most important sources of flavonoids were tea (48% of total intake), onions (29%), and apples (7%). Flavonoid intake did not vary between seasons; it was not correlated with total energy intake (r = 0.001), and it was only weakly correlated with the intake of vitamin A (retinol equivalents, r = 0.14), dietary fiber (r = 0.21), and vitamin C (r = 0.26). Our use of new analytic technology suggests that in the past flavonoid intake has been overestimated fivefold. However, on a milligram-per-day basis, the intake of the antioxidant flavonoids still exceeded that of the antioxidants beta-carotene and vitamin E. Thus flavonoids represent an important source of antioxidants in the human diet.
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PMID:Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands. 841 27

Seventy-five percent of esophageal cancers are alcohol related, yet alcohol is not a carcinogen. Ethanol may promote carcinogenesis via increased free radical products during its metabolism, as indicated by data from this and other studies. Ethanol is oxidized to acetaldehyde by alcohol dehydrogenase, catalase and the microsomal ethanol oxidizing system (MEOS). Free radicals (FR) are released during the oxidation of ethanol by the MEOS. An increased formation of FR in tissues would increase their oxidative stress and may increase their susceptibility for developing chemically induced cancers. FR and some FR products can rapidly react with biological materials, i.e. lipids, proteins and nucleic acids, forming toxic products. This study focuses on the effects of FR and/or FR products on cancer promotion during alcohol metabolism. Eight groups of mice were fed nutritionally adequate diets supplemented with vitamin E and/or ethanol. Some groups of mice were also orally gavaged with N-nitrosomethylbenzylamine (NMBzA), an esophageal carcinogen. Following the feeding of the various diets for 22 weeks, livers and esophagi were removed and the FR burden in the liver measured by the presence of lipid peroxide products and the number of tumors in each esophagus determined. These studies indicate that a linear relationship exists between the increasing number of esophageal tumors and increasing levels of lipid peroxide products that are formed during FR activity. These results show that FR and/or FR products are the cancer promoters during ethanol metabolism, since diets supplemented with high levels of vitamin E, which inhibits ethanol-induced FR activity and the formation of FR products, suppress the promotion of cancer by ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of cancer growth by vitamin E and alcohol. 847 Oct 82

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

We have previously reported that oxy radicals can contribute to the enhancing effect of glycerol on 4-nitroquinoline 1-oxide (4NQO)-induced lung tumorigenesis in ddY mice. In this study, we established that feeding high doses of vitamin E to male ddY mice treated with 4NQO plus glycerol could reduce glycerol-enhanced lung tumorigenesis, due to the inhibition of glycerol-induced oxidative stress on the pulmonary nuclei. At 4 weeks after 4NQO injection (10 mg/kg, s.c.), the levels of nuclear thiobarbituric acid reactive substances and oxidative damage to DNA in the lungs of mice treated with 4NQO plus glycerol (5% solution as drinking water) were significantly higher than those in mice treated with 4NQO. The glycerol-induced increase was completely inhibited when a high vitamin E diet was provided for 4 weeks after 4NQO injection. As previously reported, at 23 weeks after 4NQO administration (at the end of this experiment), the 4 week treatment with glycerol enhanced 4NQO-induced lung tumorigenesis in ddY mice. In contrast, the supply of high doses of vitamin E at 4 and 23 weeks after 4NQO injection suppressed glycerol's ability to enhance lung tumorigenesis. These results suggest that vitamin E is useful in protecting against oxy radical-enhanced lung tumorigenesis in mice.
Carcinogenesis 1993 Jun
PMID:Is vitamin E a useful agent to protect against oxy radical-promoted lung tumorigenesis in ddY mice? 850 98

The induction of oxidative stress in the target tissue has been proposed as a possible mechanism of action for nongenotoxic carcinogens. A variety of nongenotoxic hepatocarcinogens including peroxisome proliferators, organochlorines, barbiturates, and metals have been shown to produce an increase in reactive oxygen species (ROS) in the liver. Our group has examined the induction of oxidative stress by the organochlorine mouse hepatic carcinogen, dieldrin. Using a salicylate spin trap assay, dieldrin was found to produce mouse liver-specific increases in ROS in cultured hepatocytes. Increased amounts of hepatic 8-hydroxy-2'-deoxyguanosine and malondialdehyde (MDA) and decreased levels of cellular antioxidants were also seen in cultured mouse hepatocytes following dieldrin treatment. In subchronically dieldrin-treated mice and rats, hepatic vitamin E (Vit E) was decreased correlated with dieldrin dose. While Vit E levels were decreased in both rats and mice, the normal lower levels of Vit E in the mouse resulted in a subsequent oxidative stress, evidenced by an increase in MDA formation in the mouse liver. Dieldrin also produced a dose-dependent increase in DNA synthesis in the mouse (not the rat) following subchronic treatment. These effects seen in both cells in culture and in vivo were species specific, organ specific, and dose dependent which directly correlated with the observed pattern of cancer induction for dieldrin in rodents (mouse liver-specific). These findings support a possible role for the induction of oxidative stress in nongenotoxic hepatic carcinogenesis possibly through modulation of gene expression.
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PMID:Oxidative stress in nongenotoxic carcinogenesis. 859 27

There is a complex interaction between environmental/dietary factors and genetics underlying the pathogenesis of colon carcinogenesis. Little data exist concerning the impact of diet on the phenotypic expression of genetically linked colon cancer. As a result, it has been difficult to develop rationally designed dietary intervention studies in first-degree relatives of patients with established familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) and other familial colon cancer syndromes. Only 2 double-blinded, placebo-controlled trials have been published concerning the use of preventive strategies in patients with genetically inherited colorectal cancer syndromes, both in patients with FAP. One study evaluated the effects of vitamin C plus vitamin E with or without a high-dose wheat bran fiber supplement on the recurrence of rectal adenomas. Over a 48-month intervention period, only the wheat bran fiber intervention significantly reduced polyp growth. A second study reported that intervention with the NSAID sulindac for 9 months in young patients with FAP resulted in a significant reduction in both polyp number and size in the rectosigmoid colon. All of the large-scale (i.e., >500 randomized participants) phase III nutrient or chemopreventive agent intervention studies thus far have targeted participants with a history of non-familial, sporadic colorectal adenomas. Current clinical adenoma trials do not measure whether the regimen being tested can prevent genotoxic events occurring in early stages of abnormal cell development that contribute to the eventual formation of adenomas nor whether the agent(s) can inhibit events occurring during the progression of adenomas to carcinomas. Therefore, future clinical trial designs may have to consider (i) lengthening the clinical trial period before adenomas develop, (ii) testing at early patient ages and/or (iii) measuring the growth of adenomas as they progress to carcinomas.
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PMID:Genetic screening for colorectal cancer and intervention. 860 65


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