Comparison of metabolic effects of carbon tetrachloride and 1,2-dichloroethane added in vitro to slices of rat liver

Abstract

Carbon tetrachloride and 1,2-dichloroethane (1,2DCE) were added in vitro to freshly prepared slices of rat liver and the time- and concentration-dependence of their toxic effects on several metabolic parameters determined. With each agent, the most sensitive effect was an increase of malondialdehyde production by a microsomal preparation isolated from the treated slices. The next most sensitive parameter was the inhibition of amino acid incorporation into slice proteins, followed by inhibition of net K + accumulation and the induction of early necrotic changes, as indicated by loss of histological staining with azure II. Substantially greater exposures were required to reduce cellular ATP and to initiate entry of Ca 2+. This sequence was similar with both agents, but CCl 4 was the more potent in each case. When added in combinations of submaximally effective concentrations, the two agents produced at least additive inhibitions of protein synthesis and K + accumulation. We conclude that metabolic effects in liver slices can be a useful in vitro test for potential toxicity of chlorinated hydrocarbons. Amino acid incorporation and K + transport are the most convenient indicator systems, combining considerable sensitivity to relatively low levels of exposure with convenience of measurement.