Toxic liver injury. Inhibition of protein synthesis in rat liver by dimethylnitrosamine in vivo

Publisher Website
Google Scholar
Abstract
A study was made of the turnover of some rat-liver constituents during the early stages of toxic liver necrosis produced by dimethylnitrosamine. Incorporation of (Cl4) amino acids into liver proteins was markedly reduced at 3 and 6 hours after a necrotizing dose of dimethylnitrosamine (50 mg/kg body weight). This reduction occurred to about the same extent in the different subcellular fractions of liver. Incorporation into kidney and spleen proteins was unimpaired. The concentration of free amino acids in the liver was not significantly altered 3 hours after dimethylnitrosamine, nor was the incorporation of labeled amino acids into the free amino acid pool. The incorporation into the liver proteins in these animals was reduced by about 50%. Incorporation of P32 into phosphorus-containing fractions of rat liver was studied during the period 4 to 6 hours after the necrotizing dose of dimethylnitrosamine. There was no significant alteration in the relative specific activities of the acid-soluble phosphorus, the lipid phosphorus and the residual phosphorus (alkali-soluble phosphorus). Incorporation into partially purified ribonucleic acid was significantly reduced during this period. The concentrations of plasma inorganic phosphorus, liver acid-soluble phosphorus and lipid phosphorus were not significantly changed 6 hours after dimethylnitrosamine. The concentration of residual phosphorus (alkali-soluble phosphorus) was significantly reduced. The concentration of liver glycogen was not significantly altered 3 hours after the same dose of dimethylnitrosamine. The results are discussed in relation to morphological and metabolic findings published elsewhere. It is suggested that the initial damaging action of dimethylnitrosamine on the liver cell may be on the microsomal structures.