The repression and derepression of hepatic tyrosine aminotransferase by carcinogens.
Like hydrocortisone, a single carcinogenic dose of dimethylnitrosamine (50 mg/kg) initiates the induction cycle for hepatic tyrosine aminotransferase in adrenalectomized rats. However, following this initial induction in the presence of dimethylnitrosamine, the enzyme becomes refractory to reinduction by known inducers. The administration of thioacetamide to either adrenalectomized or intact rats leads to an immediate and progressive loss of inducibility by hydrocortisone, dibutyrylcyclic AMP or dimethylnitrosamine. Although the thioacetamide-induced repression was not reversed even up to 10 weekds after the cessation of treatment, it was reversed after the induction of liver regeneration. Both the carcinogen-mediated induction and repression of tyrosine aminotransferase appears to occur by mechanisms which do not involve the corticosteroid-binding proteins which normally mediate the induction by glucocorticoids.
The repression and derepression of hepatic tyrosine aminotransferase by carcinogens. Like hydrocortisone, a single carcinogenic dose of dimethylnitrosamine (50 mg/kg) initiates the induction cycle for hepatic tyrosine aminotransferase in adrenalectomized rats. However, following this initial induction in the presence of dimethylnitrosamine, the enzyme becomes refractory to reinduction by known inducers. The administration of thioacetamide to either adrenalectomized or intact rats leads to an immediate and progressive loss of inducibility by hydrocortisone, dibutyrylcyclic AMP or dimethylnitrosamine. Although the thioacetamide-induced repression was not reversed even up to 10 weekds after the cessation of treatment, it was reversed after the induction of liver regeneration. Both the carcinogen-mediated induction and repression of tyrosine aminotransferase appears to occur by mechanisms which do not involve the corticosteroid-binding proteins which normally mediate the induction by glucocorticoids.