[Effect of tetracyclines on protein metabolism in cultured hepatocytes].

The purpose of the present study was to investigate the effect of Tetracyclines (TCs); Minocycline (MINO), Tetracycline (TC), Demethylchlortetracycline (DMTC), Pyrrolidinomethyltetracycline (PMTC), on amino acid transport and incorporation in hepatocytes. By the use of liver cell culture, this study was done without complex interactions taking place in whole animals. MINO inhibited most strongly both uptake and incorporation into cellular protein of 3H-L-leucine in cultures of a clonal strain of rat hepatoma cells. This inhibitory effect of MINO was proved to be dose-dependent and reversible. The order of the inhibitory effect of TCs was follows; MINO, DMTC, TC, PMTC. But this inhibitory effect showed no significant correlation with the intracellular content of TCs. Almost the same degree as the inhibition by TCs of 3H-L-leucine incorporation into protein was noted when measuring total intracellular 3H-L-leucine reduction by TCs. These results suggest that the TCs-induced liver dysfunction is probably due to the inhibitory effect of TCs on amino acids uptake followed by inhibition of protein synthesis.