Permanent decrease in activity of ornithine decarboxylase antizyme in rat liver during chemical hepatocarcinogenesis.
This study was undertaken to determine whether or not there is failure of cellular control of L-ornithine decarboxylase activity by its antizyme, the only known natural intracellular inhibitor protein for L-ornithine decarboxylase activity, in rat liver during hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene. The formation of hepatic ornithine decarboxylase antizyme was elicited by i.p. injections of putrescine into rats fed a basal diet and rats fed the carcinogenic diet. The activities of both hepatic ornithine decarboxylase and hepatic ornithine decarboxylase antizyme were measured every month for five months, i.e., until hepatoma was fully developed. During azo-dye hepatocarcinogenesis and in fully developed hepatoma the activity of hepatic ornithine decarboxylase antizyme was always significantly lower than in normal resting liver, with minima at the second and the third months. The hepatoma does not synthesize ornithine decarboxylase antizyme more slowly than normal liver, since the difference could be neither abolished nor lessened by lengthening the time available for antizyme formation. Our results strongly suggest that the high intracellular putrescine levels in the livers of rats during 3'-methyl-4-dimethylaminoazobenzene hepatocarcinogenesis do not exert their normal control on hepatic ornithine decarboxylase activity because of a relative inability of these preneoplastic or neoplastic cells to make the ornithine decarboxylase antizyme.
D000818:Animals; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D008749:Methyldimethylaminoazobenzene / Q000633:toxicity; D065108:Ornithine Decarboxylase Inhibitors; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D065108:Ornithine Decarboxylase Inhibitors; D011506:Proteins; C031017:ornithine decarboxylase antizyme; D008749:Methyldimethylaminoazobenzene