Restoration of normal ornithine decarboxylase antizyme activity in rat liver after acute carcinogen treatment

Abstract

This study was undertaken to see whether or not the decrease in ornithine decarboxylase antizyme activity caused in rat liver by a hepatocarcinogen could be reversed. Thioacetamide was administered only once, in a single i.p. injection and at a non-carcinogenic, non-necrogenic dose. The activities of both hepatic ornithine decarboxylase and hepatic ornithine decarboxylase antizyme were measured at intervals of hours after the injection of thioacetamide. The hepatic ornithine decarboxylase antizyme in thioacetamide-treated rats was minimal at 40 and 80 h after carcinogen administration. The reversal process requires a very long time, namely 450 h for normal levels of hepatic ornithine decarboxylase antizyme activity to be restored in treated rats. This time is much longer than that required to restore normal ornithine decarboxylase activity in liver of thioacetamide-treated rats. The results of this study, combined with those of the preceding paper, demonstrate that hepatocarcinogens cause a relative inability of rat liver cells to make the ornithine decarboxylase antizyme and that the irreversibility of this defect in cellular control of ornithine decarboxylase activity may be a constant feature in the neoplastic transformation of the rat liver.