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

The influence of a low methionine intake on the chemopreventive efficacy of selenomethionine versus selenite was compared in the 7,12-dimethylbenz[a]anthracene-induced mammary tumor model in rats. Animals were fed from weaning a purified 20% casein diet with or without 0.3% methionine supplementation. Selenomethionine or selenite, at a final concentration of 3 ppm of selenium (Se), was added to the diet starting 5 days after DMBA administration. Control rats continued to receive the basal diets which contained 0.1 ppm of Se. Results of the carcinogenesis experiment indicated that suboptimal dietary methionine significantly reduced the protective effect of selenomethionine in cancer prevention. In contrast, the efficacy of selenite was not affected. In rats given 3 ppm of selenomethionine, tissue Se was actually higher in those fed a diet with a suboptimal amount of methionine than in those with an adequate intake of methionine. On the other hand, dietary methionine did not influence the level of tissue Se in animals given selenite. An increase of dietary methionine to 0.6% did not enhance the efficacy of selenomethionine in cancer protection but would allow the use of a higher level of selenite without the accompanying adverse effects. The biological significance of Se utilization under suboptimal or adequate methionine intake was also assessed using the glutathione peroxidase assay in the liver of Se-deficient rats given graded levels of Se as either selenite or selenomethionine. The enzyme study demonstrated that low dietary methionine decreased the nutritional biopotency of selenomethionine in restoring glutathione peroxidase activity but not that of selenite. These experiments suggest that adequate methionine intake is required for the utilization of selenomethionine for nutritional and anticarcinogenic purposes.
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PMID:Differential effect of dietary methionine on the biopotency of selenomethionine and selenite in cancer chemoprevention. 335 61

Enzyme activities relating to H2O2 production (peroxisomal acyl-CoA oxidase) and degradation (catalase and glutathione peroxidase) were measured in the livers of male mice of the inbred strains C57BL/6J (C57) and C3H/HeJ (C3H) and their F1 hybrid, B6C3F1. Groups of the three genotypes were maintained on either a basal diet or one containing 0.1% of the peroxisome-proliferating agent, nafenopin, for six weeks. In both control and nafenopin-exposed groups, the C57 strain displayed higher acyl-CoA oxidase activity levels than the C3H mice, whereas the activity levels of catalase and glutathione peroxidase were not different for the two inbred strains. The groups of similarly fed B6C3F1 hybrids had intermediate values for acyl-CoA oxidase. Several other parameters relating to peroxisome proliferation did not differ among the three genotypes. Acyl-CoA oxidase levels in cultured hepatocytes from C57 mice were greater than those in hepatocytes obtained from the C3H strain during two days in culture and this difference was maintained for 4 days by nafenopin exposure. Acyl-CoA oxidase is central to the hypothetical H2O2 mechanism of peroxisome proliferator-induced hepatocarcinogenesis and, therefore, the genetic difference documented here may lead to a useful approach in testing this hypothesis.
Carcinogenesis 1988 Aug
PMID:Genetic differences in enzymes associated with peroxisome proliferation and hydrogen peroxide metabolism in inbred mouse strains. 340 42

An increasing body of evidence suggests that glutathione-dependent enzymes are an important factor in determining the sensitivity of tumours to cytotoxic drugs. Ten randomized normal and tumour samples from individuals with lung cancer were analysed for glutathione S-transferase isoenzyme (GST) content and glutathione peroxidase (Gpx) activity. The normal tissue samples exhibited a 5.1- and 7.0-fold variation in GST and Gpx activity respectively. High levels of the pi class, acidic Yf, GST subunit were found in all the samples, with little variation between individuals. The concentration of alpha and mu class subunits was 5- to 10-fold lower and were subject to significant individual variability. The mu class subunit identified had a faster mobility on SDS-PAGE than the hepatic GST mu standard and did not appear subject to the genetic polymorphism associated with certain members of this gene family. This suggests the presence of a novel pulmonary protein which may correspond to the rat Yn Yn protein. The normal to tumour ratio for GST activity varied significantly between the samples and tended to follow the relative expression of the mu class subunit, and to a lesser extent the alpha class GST subunit. The pi subunit was present in the normal and tumour cells in very similar concentration. The expression of the mu class GST appeared to follow the differences in GST enzymic activity and although the numbers were small appeared to segregate according to tumour type. Gpx activity was also elevated in certain tumours. Of particular interest were the two adenocarcinomas which had a 20- to 30-fold higher tumour Gpx activity.
Carcinogenesis 1988 Sep
PMID:Glutathione S-transferase isoenzymes and glutathione peroxidase activity in normal and tumour samples from human lung. 340 65

Results from in vivo and in vitro studies showing that antioxidants may act as anticarcinogens support the role of active oxygen in carcinogenesis and provide impetus for exploring the functions of dietary antioxidants in cancer prevention by using in vitro models. We examined the single and combined effects of selenium, a component of glutathione peroxidase, and vitamin E, a known antioxidant, on cell transformation induced in C3H/10T-1/2 cells by x-rays, benzo[a]pyrene, or tryptophan pyrolysate and on the levels of cellular scavenging systems and peroxide destruction. Incubation of C3H/10T-1/2 cells with 2.5 microM Na2SeO3 (selenium) or with 7 microM alpha-tocopherol succinate (vitamin E) 24 hr prior to exposure to x-rays or the chemical carcinogens resulted in an inhibition of transformation by each of the antioxidants with an additive-inhibitory action when the two nutrients were combined. Cellular pretreatment with selenium resulted in increased levels of cellular glutathione peroxidase, catalase, and nonprotein thiols (glutathione) and in an enhanced destruction of peroxide. Cells pretreated with vitamin E did not show these biochemical effects, and the combined pretreatment with vitamin E and selenium did not augment the effect of selenium on these parameters. The results support our earlier studies showing that free radical-mediated events play a role in radiation and chemically induced transformation. They indicate that selenium and vitamin E act alone and in additive fashion as radioprotecting and chemopreventing agents. The results further suggest that selenium confers protection in part by inducing or activating cellular free-radical scavenging systems and by enhancing peroxide breakdown while vitamin E appears to confer its protection by an alternate complementary mechanism.
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PMID:Selenium and vitamin E inhibit radiogenic and chemically induced transformation in vitro via different mechanisms. 345 98

In studies designed to determine the influence of dietary Se on pancreatic carcinogenesis, Syrian golden hamsters were fed unsupplemented torula yeast diet or diet supplemented with 0.1 or 5.0 ppm Se, from sodium selenite, starting at 4 weeks of age until the termination of the study. In separate groups, hamsters were given the diet supplemented with 0.1 ppm Se until 5 days after carcinogen treatment. Then they were fed either the unsupplemented diet or the diet supplemented with 5.0 ppm Se until the end of the experiment. N-Nitrosobis(2-oxopropyl)amine (BOP; CAS; 60599-38-4) treatment was given as a single sc injection of 20 mg/kg (body wt) at 8 weeks of age, and surviving hamsters were killed 50 weeks later. As a measure of Se status, glutathione peroxidase (GSHPX) activities were determined in plasma, erythrocytes, and liver. Values were elevated in animals fed higher levels of dietary Se. BOP treatment depressed plasma GSHPX at 24 hours and elevated erythrocyte and liver values at 4 weeks. Pancreatic ductular adenoma yields were inhibited with each elevation of dietary Se in female hamsters fed the diets, both before and after BOP administration, and were further inhibited in females that were fed diets containing 0.1 ppm Se before BOP administration and that were changed to the unsupplemented or 5.0-ppm-supplemented diets after BOP was given. Pancreatic ductular adenoma yields were highest in all male groups given diets of 0.1 ppm Se before BOP administration, irrespective of the Se level after BOP was fed. Adenoma yields in males were lowest in hamsters fed unsupplemented diet, both before and after BOP treatment. Pancreatic carcinoma yields were low and not influenced by dietary Se. The incidence of hepatic necrosis was elevated in BOP-treated hamsters fed the unsupplemented diet, and that of biliary cystic adenomas was highest in the group fed 0.1 ppm Se before and after BOP treatment.
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PMID:Effects of dietary selenium on bis(2-oxopropyl)nitrosamine-induced carcinogenesis in Syrian golden hamsters. 346 17

The mechanisms by which diallyl sulfide (DAS), a component of garlic oil, inhibits hepatocarcinogenicity of 1,2-dimethylhydrazine (DMH) were examined in male Fischer 344 rats. Rats were subjected to partial hepatectomy to stimulate hepatocellular proliferation required for initiation by DMH (50-200 mg/kg i.p.) given 12 h later. Initiation was assessed by the numbers of foci and nodules of hepatocytes that were positive for gamma-glutamyl transpeptidase (gamma-GT) or glutathione-S-transferase-P (GST-P) after 6 weeks promotion by orotic acid (1% in semi-purified diet). DAS at doses above 50 mg/kg (by gavage) administered 1 h before DMH (50 mg/kg) partially reduced the numbers of gamma-GT and GST-P-positive foci. By comparison, all doses of DAS (25-100 mg/kg) completely prevented liver necrosis by DMH (200 mg/kg). DAS substantially reduced macromolecular binding of [14C]DMH in cultured liver cells, but had no effect on their levels of glutathione-S-transferase, glutathione reductase or glutathione peroxidase at 18 h. These findings suggest that low dosages of DAS which reduce DMH binding appear more likely to inhibit hepatocarcinogenicity by reducing the promoting influences of post-necrotic regeneration than by preventing initiation.
Carcinogenesis 1987 Aug
PMID:Inhibition of hepatocarcinogenic responses to 1,2-dimethylhydrazine by diallyl sulfide, a component of garlic oil. 360 98

The effect of feeding benzylselenocyanate (BSC) and its sulfur analogue, benzylthiocyanate (BTC), 2 wk before, during, and until 1 wk after carcinogen administration (initiation phase) on intestinal carcinogenesis induced by azoxymethane (CAS:25843-45-2) was studied in male F344 rats. Weanling rats were raised on a semipurified diet (AIN-76A diet; control diet). Beginning at 5 wk of age, groups of animals consuming the control diet were fed one of the diets containing 25 ppm BSC or BTC. An additional group was continued on the control diet. At 7 wk of age, all animals in 3 groups, except the vehicle-treated controls, were administered s.c. injections of azoxymethane (15 mg/kg body weight, once weekly for 2 wk). Animals were continued on the control diet and BSC and BTC diets until 1 wk after carcinogen treatment, when those groups receiving BSC and BTC diets were fed the control diet until termination of the experiment. Tissue and blood plasma glutathione peroxidase activity was measured in vehicle-treated animals fed the control diet and BSC and BTC diets for 5 wk. The results indicate that body weights were comparable among the various dietary groups. BSC in the diet significantly inhibited the incidence (percentage of animals with tumors) and multiplicity (tumors/animal) of adenocarcinomas in the colon and multiplicity of adenocarcinomas in the small intestine compared to those fed the control diet. BTC in the diet had no effect on colon and small intestinal tumors. Selenium-dependent glutathione peroxidase activity was significantly increased in kidneys and colon and small intestinal mucosae of animals fed the BSC diet compared to animals fed the BTC and control diets.
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PMID:Chemoprevention of colon carcinogenesis by dietary organoselenium, benzylselenocyanate, in F344 rats. 366 91

Female F-344 rats were fed a diet containing up to 1.2% di(2-ethylhexyl)phthalate (DEHP) for 2 years, which previously resulted in hepatocarcinogenesis under bioassay conditions. Peroxisome proliferation, decreased glutathione peroxidase activity, and lipofuscin accumulation were all associated with prolonged feeding of 1.2% DEHP and induction of hepatic neoplasia. These results establish a potential role for persistent peroxisome proliferation and oxidative injury in the hepatocarcinogenicity of dietary DEHP. Increased hepatocellular proliferation and hepatomegaly were not detected. DEHP feeding did not increase the volume density of basophilic or ATPase-deficient foci of altered hepatocytes, suggesting that these lesions are not suitable indicators of DEHP carcinogenesis.
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PMID:Association of persistent peroxisome proliferation and oxidative injury with hepatocarcinogenicity in female F-344 rats fed di(2-ethylhexyl)phthalate for 2 years. 369 May 5

These studies were undertaken to assess the effect of dietary selenium on glutathione-related enzyme activities in the liver and kidney and on hepatic drug metabolism. The intent was to study underlying mechanisms of selenium-induced beneficial effects in some models of hepatoxicity and carcinogenesis. Dietary selenium, as sodium selenite, was incorporated into a torula yeast basal diet (0.02 ppm selenium) and fed to male rats at supplementation levels of 0.0-5.0 ppm selenium for periods of three or six weeks. Additionally, a commercial cereal-based diet (CD, 0.05-0.08 ppm selenium) was compared to the experimentally defined diet (DD) supplemented with approximately the same amount of selenium. Liver and kidney glutathione peroxidase activity essentially plateaued at levels of selenium of 0.1 ppm and greater. CD- and DD-fed animals had hepatic and renal glutathione peroxidase activities which were similar. Glutathione S-transferase activity in liver, but not kidney, increased with increasing supplements of selenium. Glutathione S-transferase activities in CD- and DD-fed rats were not different. Cytochrome P-450 content and associated oxidative drug metabolism activities were relatively unmodified by selenium. Overall, dietary selenium appeared to act by enhancing potential conjugative detoxication pathway, rather than by decreasing the potential activation of chemicals via the hepatic cytochrome P-450 system.
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PMID:Differential effects of dietary selenium on hepatic and renal glutathione-related enzymes and on hepatic microsomal drug metabolism in the rat. 369 24

Selenium (Se) compounds have shown an inhibitory effect on chemically induced tumours in several laboratory models and there is an inverse epidemiological relationship between Se status and certain types of cancer. Little is known about the influence of Se on the development of stomach cancer. Three different forms of dietary Se, selenomethionine, sodium selenite, and high-selenium yeast were investigated as possible inhibitors of benzo(a)pyrene-induced forestomach tumours in mice. The effects of sodium selenite in combination with vitamin E, and of Se-deficiency were also studied. None of the dietary modifications had any effect on tumour incidence or number. Marked elevations of whole-blood glutathione peroxidase (GSH-Px) activities were observed in animals supplemented with all Se-compounds. High-selenium yeast caused the largest increase of GSH-Px activity followed by sodium selenite and selenomethionine. The results indicate that the inhibitory effect of Se on carcinogenesis may be specific with respect to organ site or tumour cell examined.
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PMID:Effects of dietary selenium compounds on benzo (a)-pyrene-induced forestomach tumours and whole-blood glutathione peroxidase activities in C3H mice. 375 57


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