Lipid peroxidation in the liver of carcinogen-resistant rats.
Recently, we developed a new strain of rats that exhibit marked resistance to the hepatotoxic and carcinogenic actions of 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) and some other carcinogens. In this work, we compared lipid peroxidation in the liver of these carcinogen-resistant (R) rats and the parental Donryu strain rats that are sensitive (S) to hazardous actions of these carcinogens. The liver microsomal fractions of the R group contained less amounts of polyunsaturated fatty acids. Microsomal lipid peroxidation in the presence of exogenous NADPH was much lower in R rats than in S rats. Liver microsomes of R rats were much less active than those of S rats also in producing 4-hydroxynonenal, carbonyl compounds and conjugated diene. The hepatic contents of ascorbic acid, glutathione, alpha-tocopherol and coenzyme Q in the R rats were similar to those in S rats. The activities of the free radical scavenger enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), in the two groups were also similar. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are both thought to function in disposal of these cytotoxic aldehydes. The liver microsomal and mitochondrial ALDH activities of the two groups were similar. The ADH activity of the liver cytosolic fraction of R rats was nearly twice that of S rats, as measured with 4-hydroxynonenal as substrate. The higher ADH activity may explain the decreased lipid peroxidation in R rats at least partly, if this enzyme is involved in lipid peroxidation.
Hammad
H
H
Department of Oncology, Osaka University Medical School, Japan.
Higashi
T
T
Tateishi
N
N
Hanatani
M
M
Sakamoto
Y
Y
D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D004351:Drug Resistance; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005296:Ferrous Compounds / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism*; D008297:Male; D008749:Methyldimethylaminoazobenzene / Q000633:toxicity; D008862:Microsomes, Liver / Q000378:metabolism; D008930:Mitochondria, Liver / Q000201:enzymology; D009249:NADP / Q000378:metabolism / Q000494:pharmacology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D013858:Thiobarbiturates
D002273:Carcinogens; D005231:Fatty Acids, Unsaturated; D005296:Ferrous Compounds; D013858:Thiobarbiturates; D009249:NADP; D008749:Methyldimethylaminoazobenzene; D000426:Alcohol Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000444:Aldehyde Dehydrogenase; D009251:NADPH-Ferrihemoprotein Reductase; C029684:thiobarbituric acid