Biochemical alterations in hepatic tissue of ethionine and N-nitrosodimethylamine treated mice, and in a transplantable tumor of rat.

Abstract

Considerably lowere CO2-14C production from the degradative pathway of thymidine -14C utilization was observed in the hepatic tissues of mice (C3H) that recieved multiple intraperitoneal doses of ethionine (400 mg/kg on day 1 5, 9, 13, 17, 21 and 25). While the incorporation of thymidine -14C into DNA was unchanged throughout this period, the tRNA methylase activity of these mice receiving multiple doses of ethionine was significantly lowered at the final sacrifice. When a lower single dose of ethionine (80 mg/kg) was given to mice, the depression of CO2-14C produced from thymidine -14C utilization was less pronounced.Transplantable dimethylaminobenz(a)anthracene (DMBA) induced manunary tumor of rat showed both increased incorporation of thymidine -14C into DNA and t-RNA methylase activity. Also, transplantable Morris hepatoma, although not available for testing in this study, shares a similar pattern of thymidine utilization with transplantable mammary tumor and in general, all other transplantable tumors. In contrast to transplantable tumors N-nitrosodimethylamine (NDMA) induced hepatomas of mice showed no statistically significant alteration in their utilization of thymidine -14C.The known hepatotoxins, bromobenzene and carbon tetra-chloride, when administered to rats in a single dose all lowered the heptatic CO2-14C production from thymidine -14C utilization as compared to non-treated controls (p<0.001, p<0.01 respectively). The implication of these findings is discussed.