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 (CCl(4)) and trichloroethylene (TRI). TRI is known to potentiate CCl(4)-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 CCl(4) 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 CCl(4) produced a significant elevation in lactate dehydrogenase while other markers remained statistically unaffected. CCl(4) toxicity was potentiated in the presence of TRI. Ureogenesis remained unaltered in cultures after exposure to CCl(4) 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.
Kefalas
V
V
National Institute of Occupational Health and Safety, The University of Sydney, NSW, Australia.
Stacey
N H
NH