Comparative cytotoxicity of bromobenzene in primary cultures of rat and hamster hepatocytes and its relation to biotransformation.
Primary cultures of rat and hamster hepatocytes were exposed to 0.5-2 mm-bromobenzene (BrB). Exposure to 2 mm-BrB within 2 hr after isolation caused cellular damage to hepatocytes from both species. Exposure to BrB also resulted in reduced glutathione (GSH) levels. In hamster hepatocytes, GSH was depleted by 60-85% with 0.5 mm-BrB, whereas in rat hepatocytes 2 mm caused a GSH depletion of about 50%. Liver cell cultures from both species converted BrB into three bromophenols. Hamster hepatocytes and microsomes appeared to metabolize BrB more rapidly than those from rat liver. However, in hamster hepatocytes at BrB concentrations of less than 2 mm no cytotoxicity could be detected, despite a rapid biotransformation of BrB and a vast depletion of glutathione; both factors are thought to be prerequisites for BrB-induced hepatotoxicity. The results of this comparative in vitro study emphasize the importance of detoxification mechanisms other than conjugation to GSH, such as a high epoxide hydrolase activity, in the determination of sensitivity to BrB.
Mennes
W C
WC
Research Institute of Toxicology, University of Utrecht, PO Box 80.176, Utrecht, The Netherlands.
van Holsteijn
C W
CW
Noordhoek
J
J
Blaauboer
B J
BJ