USE OF PRIMARY CULTURES OF RAT HEPATOCYTES TO STUDY INTERACTIVE TOXICITY - CARBON-TETRACHLORIDE AND TRICHLOROETHYLENE

The use of primary cultures of rat hepatocytes as an experimental model for interactive toxicity studies was evaluated by studying carbon tetrachloride (CCl4) and trichloroethylene (TRI). TRI is known to potentiate CCl4-induced hepatotoxicity in vivo as well as in vitro utilizing rat hepatocyte suspensions and plasma membranes. When hepatocytes were cultured in a sealed system for 48 hr, the presence of TRI and CCl4 induced enzyme leakage, lipid peroxidation and an increase in lactate to pyruvate ratios significantly greater than seen in response to each halocarbon alone. Singly administered CCl4 produced a significant elevation in lactate dehydrogenase while other markers remained statistically unaffected. CCl4 toxicity was potentiated in the presence of TRI. Ureogenesis remained unaltered in cultures after exposure to CCl4 and TRI whether dosed singly or in combination. The positive interaction in toxicity and peroxidation of lipids is consistent with the findings in short-term in vitro systems as well as in vivo, thus indicating the suitability of primary cultures of rat hepatocytes for such studies.