Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three nitroparaffins (nitroethane, 1-nitropropane, and 2-nitropropane) were studied in the Salmonella typhimurium/mammalian microsome (Ames) test, with and without microsomal activation systems. Nitroethane and 2-nitropropane also were studied in an in vivo mutagenic (micronucleus) test. These studies were undertaken because these solvents are widely used in the chemical and pharmaceutical industries and 2-nitropropane was reported to cause liver cancer in rats exposed by the inhalation route. Neither nitroethane nor 1-nitropropane was active in the Ames test with Salmonella tester-strains TA1537, TA92, TA98, or TA100. However, 2-nitropropane produced a significant increase in revertants in all of these tester strains, particularly strain TA100, where 3 microliter/plate doubled the number of revertants in the presence of microsomal enzymes. Negative results were obtained with both nitroethane and 2-nitropropane in micronucleus tests. These studies have shown that 2-nitropropane has the potential for causing point mutations in a microbial test system. However, this compound probably will not cause a chromosome mutation of the clastogenic type.
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PMID:Mutagenic evaluation of nitroparaffins in the Salmonella typhimurium/mammalian-microsome test and the micronucleus test. 39 19

The influence of nutritional factors on aflatoxin B1 (AFB1)-induced liver tumours was investigated in rats. When a dose of 500 micrograms AFB1/kg body weight was given to rats in the absence of any anticarcinogen, 80 per cent of the rats developed liver tumours as compared to 0 to 40 per cent in those which received anticarcinogens. While beta-carotene totally inhibited the development of liver tumours ascorbic acid, selenium, and uric acid reduced the percentages of tumour-bearing rats to 13 per cent each. GSH and vitamin E also reduced these percentages to 20 and 40 per cent respectively. The reduction of tumour incidence by each anticarcinogen was associated with induction of increased microsomal enzyme activity. Inhibition of AFB1-induced liver cancer development thus seems to occur through microsomal enzyme induction and AFB1 activation.
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PMID:Association of reduction of AFB1-induced liver tumours by antioxidants with increased activity of microsomal enzymes. 212 79

The tissues of hepatocellular carcinoma were operatively resected from six patients. All four components of the systems of microsomal cytochrome P-450-linked monooxygenase of the tissues were investigated and compared to those of normal liver tissue. The concentrations of cytochromes P-450, P-420 and b5 were measured optically and the concentrations of all components except cytochrome P-450 were measured by the Western blotting method followed by immunochemical staining. In microsomes of hepatocellular carcinoma tissues, there was as much cytochrome P-450 and other redox components as in the normal liver tissues, but cytochrome P-450 in liver cancer tissues was unstable and easily converted to cytochrome P-420. The specific activities of NADPH- and NADH-ferricyanide and cytochrome c reductase of each sample were also measured. In the microsomes of the cancer tissues, the specific activities were remarkably reduced compared with those of normal liver tissues. The lipid compositions of the microsomes and the phospholipid/cholesterol ratios (w/w) were 13.1 +/- 3.13 in the cancer tissues and 43.0 +/- 6.74 in normal liver tissues. This difference of the lipid composition elucidates the instability of cytochrome P-450 molecules and the inefficiency of the electron transport of cytochrome P-450-linked monooxygenase systems.
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PMID:Microsomal cytochrome P-450-linked monooxygenase systems and lipid composition of human hepatocellular carcinoma. 254 14

A long-term study, using male Wistar rats, was initiated to determine whether the effects of dietary constituents on AFB1-induced liver cancer could be associated with altered microsomal enzyme activity. They were maintained on mice pellets mixed with specific dietary constituents for 7 days and then given a single carcinogenic dose of AFB1 (500 micrograms/rat). After three months, the dietary constituents were discontinued and the animals were left on mice pellets and drinking water only for a period of about 20 months. At the end of the trial period, it was observed that dietary mixtures containing small quantities of either beta-carotene, ascorbic acid, GSH, vitamin E, selenium salt, or uric acid, effectively inhibited the development of AFB1-induced liver cancer and induced increased microsomal enzyme activity. Whereas beta-carotene and uric acid were the most effective inhibitors, vitamin E was the least, yet a significant inhibitor of liver cancer. Hepatic levels of cytochrome P-450, aniline hydroxylase and chlorpromazine demethylase were significantly induced in rats fed fortified food followed by AFB1 treatment than in control animals. The inhibition of liver cancer by dietary factors was probably due to their ability to induce the activity of hepatic microsomal enzymes. Increased enzyme activity could lead to rapid activation of AFB1 metabolism, resulting in loss of activated AFB1 metabolites that attack cell components. Inhibition of liver cancer is therefore associated with induction of increased microsomal enzyme activity.
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PMID:Inhibition of AFB1-induced liver cancer and induction of increased microsomal enzyme activity by dietary constituents. 261 10

It has been reported that p.o. administration of diallyl sulfide (DAS), a naturally occurring component of garlic (Allium sativum), inhibits 1,2-dimethylhydrazine-induced colon and liver cancer in rodents. A possible mechanism for this protective effect is inhibition of hepatic activation of the procarcinogen. The effect of DAS on P450IIE1, an isozyme of cytochrome P-450 which is active in the oxidative metabolism of dimethylhydrazine, was conveniently assayed in the present study by determination of N-dimethylnitrosamine demethylase (NDMAd) activity at 1 mM N-dimethylnitrosamine in Sprague-Dawley rat liver microsomal incubations. DAS was found to be a competitive inhibitor of NDMAd, in contrast to the irreversible inactivation of NDMAd produced by carbon tetrachloride incubated under similar conditions. The inhibition by DAS of the demethylation of several substrates was selective. The thioether was most potent against N-dimethylnitrosamine, less effective against N-nitrosomethylbenzylamine, and essentially ineffective against benzphetamine and ethylmorphine. Microsomes prepared at 3 h after DAS administration (200 mg/kg in corn oil intragastrically) showed moderate inhibition (less than 30% inhibition compared to control microsomes) of several demethylase activities; however, microsomes prepared 18 h posttreatment showed a marked decrease (about 80% inhibition compared to controls) in NDMAd activity, minor effects on other demethylase activities, and a 6-fold increase in pentoxyresorufin dealkylation. These trends at 18 h agreed with immunoblot analyses which showed suppression in the level of P450IIE1 and an elevation in P450IIB1. The selective inhibition of P450IIE1 activity and suppression of its level in microsomes may contribute to the reported chemoprotective effects of DAS.
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PMID:Effect of diallyl sulfide on rat liver microsomal nitrosamine metabolism and other monooxygenase activities. 316 46

Most cancers of the upper aero-digestive tract are related to alcohol consumption. For the mouth, oesophagus and larynx a positive dose-response relationship has been observed, as well as a combination effect with tobacco smoking--according to a multiplicative model in the case of the oesophagus. Nutritional factors also play a role. For other cancer sites, the role of alcohol is controversial, except for primary liver cancer which often develops on a cirrhotic liver. The mechanisms by which alcohol increases cancer risk are still obscure. It is not considered to be a carcinogen by itself but rather as a co-carcinogen, facilitating or enhancing the role of other carcinogens. Another mechanism might be the induction of microsomal enzymes activating pro-carcinogens. As in the case for smoking, prevention can be achieved by abstention or reduction of consumption. This has to be considered seriously in countries where alcohol consumption is increasing.
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PMID:Cancer risks derived from alcohol. 332 86

Hepatocyte nodules, a characteristic early step in the development of liver cancer in rats, has a distinctive resistance phenotype including a large decrease in total cytochromes P-450 and in two isozymes induced by phenobarbital and two by 3-methylcholanthrene. In this study, it has been observed that the nodules show a large decrease in an additional cytochrome P-450, cytochrome P-452, which is very active in the hydroxylation of lauric acid at C-11 and C-12. The decrease in activity of this microsomal cytochrome P-452 is of the same order of magnitude as the decreases in the other cytochrome P-450 components. These observations are consistent with the hypothesis that there is some more basic alteration in the synthesis or availability of heme and that the changes in the activities of the cytochromes P-450 are secondary.
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PMID:Decreased expression of cytochrome P-452 in the resistance phenotype characteristic of putative preneoplastic hepatocyte nodules during hepatocarcinogenesis. 336 59

Previous studies in our laboratory have shown that the sex-differentiated metabolism of 4-androstene-3,17-dione and of several other steroid hormones in adult rat liver is "feminized" following neonatal castration of male rats, due to an influence via the hypothalamo-pituitary-liver axis. The metabolism of many xenobiotics is also sex differentiated, and an important question is whether endocrine ablations might alter hepatic carcinogen metabolism in a way explaining, for example, the decreased tendency of castrated male rats [Y.C. Toh, In: Shanmagarathnam et al. (eds.), Liver Cancer, Cancer Problems in Asian Countries, Proceedings of the Second Asian Cancer Conference, pp. 167-171. Singapore: Singapore Cancer Society, 1976] to form liver tumors following 2-acetylaminofluorene treatment. The results presented in this paper clearly show that neonatal castration of male rats, much more efficiently than adult castration, feminizes the cytochrome P-450-dependent, sex-differentiated, liver microsomal formation of 7-hydroxy-2-acetylaminofluorene, 9-hydroxy-2-acetylaminofluorene, 5-hydroxy-2-acetylaminofluorene, 1-hydroxy-2-acetylaminofluorene, and N-hydroxy-2-acetylaminofluorene from 2-acetylaminofluorene as well as the total microsomal formation of benzo(a)pyrene metabolites (male greater than female). O-Deethylation of 7-ethoxyresorufin was neither sex differentiated nor affected by castration. The capacity for in vitro sulfation of N-hydroxy-2-acetylaminofluorene in the postmicrosomal supernatant, markedly sex differentiated in the rat (male greater than female), was completely feminized by neonatal but not by adult castration. The results suggest that the influence of endocrine ablations on chemical carcinogenesis in rat liver might be mediated via the hypothalamo-pituitary regulation of certain pathways of hepatic xenobiotic metabolism.
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PMID:Effects of neonatal and adult castration on the in vitro metabolism of steroids and xenobiotics in rat liver. 375 65

Certain strains of Salmonella typhimurium and Escherichia coli, particularly those which are very sensitive to u.v. light, are killed when incubated with rat liver mixed function oxidases and aflatoxin B(1). UvrA or recA strains of E. coli are more susceptible than the wild-type strain, while the double mutant uvrA recA is the most sensitive strain yet tested. The aflatoxin B(1) metabolite is also able to induce reverse mutations in 2 histidine auxotrophic strains of S. typhimurium, one strain of which is reverted specifically by frame shift mutagens and the other by agents inducing base pair substitutions.Pretreatment of rats with either 3-methylcholanthrene or benzo(a)pyrene, both inducers of liver microsomal mixed function oxidases, did not alter the amount of lethal aflatoxin B(1) metabolite formed, whereas an increase was observed after phenobarbitone pretreatment. Addition of the nucleophiles methionine, cysteine, glutathione, sodium thiosulphate or sodium sulphide, or the epoxide hydrase inhibitor, cyclohexene oxide to the toxicity assay medium did not alter bacterial killing by the aflatoxin B(1) metabolite. 2,3-Dimercaptopropanol had some protective action.Toxic metabolites were also formed when 5-methoxysterigmatocystin, O-methylsterigmatocystin, parasiticol or versicolorin A, but not vericolorin B, were incubated with mixed function oxidases. The relationship between the metabolite of aflatoxin B(1) lethal to bacteria and that which initiates liver cancer is discussed.
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PMID:Induction of mutations in DNA-repair deficient bacteria by a liver microsomal metabolite of aflatoxin B1. 459 23

Changes of glycylproline dipeptidyl aminopeptidase (GPDA) and gamma-glutamyl transpeptidase (gamma-GTP) activities were compared in the serum and liver tissue of rats with hepatic cancer induced by 3'-methyl DAB. Serum glycylproline dipeptidyl aminopeptidase activity in rats with the azo dye-induced hepatic cancer was significantly higher than that in healthy rats, but the increase was not so extensive compared with that of gamma-glutamyl transpeptidase. The specific activity of glycylproline dipeptidyl aminopeptidase was decrease in the microsomal fraction and increased in the supernatant fraction of hepatic cancer tissue, whereas that of gamma-glutamyl transpeptidase was increased in both microsomal and supernatant fractions. These results suggest that the mechanisms, whereby serum activities of these two enzymes were increased in rats with hepatic cancer, were different from each other.
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PMID:Serum and liver glycylproline dipeptidyl aminopeptidase activity in rats with experimental hepatic cancer. 610 82


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