Decrease in L-type pyruvate kinase activity in rat liver by some promoters of hepatocarcinogenesis.
A probably promoter-specific decrease of L-type pyruvate kinase (L-PK) in Wistar rat liver is described. The possibility of utilizing the decrease in L-PK activity for screening of hepatic promoters is discussed. A significantly decreased level of activity of L-PK was observed during continuous feedings of the hepatocarcinogen 3'-methyl-4-dimethylaminoazobenzene [(3'-MeDAB) CAS: 55-80-1], which initiates and promotes hepatocarcinogenesis, and of the known hepatic promoters phenobarbital [(PB) CAS: 50-06-6] and dichlorodiphenyltrichloroethane (CAS: 50-29-3) for at least 4 weeks. In contrast, if it occurred, the decrease in L-PK activity by the nonpromoting agents amobarbital (CAS: 57-43-2) and diphenylhydantoin. (CAS: 57-41-0) was temporary and almost overcome by the 4th week. The depression of L-PK activity caused by PB was reversible, was inversely correlated with PB concentration in the diet, and seemed to be organ-specific. Although hepatic promoters lowered L-PK activity in this study, data are so limited that a much more extensive study is necessary before a general conclusion can be drawn. In contrast to L-PK activity, the activity of K-type pyruvate kinase (K-PK) was induced by injections of the carcinogen diethylnitrosamine (CAS: 55-18-5) or the hepatotoxin CCl4 (CAS: 56-23-5) or by the feeding of 3'-MeDAB. However, feeding of PB or 2-methyl-4-dimethylaminoazobenzene (CAS: 54-88-6), which initiates but does not promote hepatocarcinogenesis, did not increase K-PK activity.
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology; D002273:Carcinogens / Q000633:toxicity*; D004052:Diethylnitrosamine / Q000633:toxicity; D007527:Isoenzymes / Q000378:metabolism*; D007536:Isomerism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D008297:Male; D008749:Methyldimethylaminoazobenzene / Q000633:toxicity; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000633:toxicity; D011770:Pyruvate Kinase / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012439:Saccharin / Q000633:toxicity
D002273:Carcinogens; D007527:Isoenzymes; D004052:Diethylnitrosamine; C002432:2-methyl-4-dimethylaminoazobenzene; D008749:Methyldimethylaminoazobenzene; D010672:Phenytoin; D011770:Pyruvate Kinase; D012439:Saccharin; D010634:Phenobarbital