INTERINDIVIDUAL VARIATION IN BIOTRANSFORMATION AND CYTOTOXICITY OF BROMOBENZENE AS DETERMINED IN PRIMARY HEPATOCYTE CULTURES DERIVED FROM MONKEY AND HUMAN LIVER

1 Bromobenzene-evoked hepatotoxicity resulting from cytochrome P450-me diated epoxidation has been studied extensively in rodents in vivo and in rodent hepatocytes. In this paper we present data concerning the f ormation of bromphenols, glutathione (GSH) depletion and cytotoxicity observed in primate hepatocytes in primary culture after exposure to b romobenzene (BrB). 2 After pre-incubation for 2 or 24 h, hepatocytes w ere exposed to BrB in concentrations up to 2 mM for 4 or 24 h. 3 In bo th human and cynomolgus monkey hepatocytes BrB cytotoxicity and GSH de pletion were found after exposure to 2 mM BrB. The degree of the obser ved effects was not influenced by the duration of pre-incubation and/o r exposure periods. 4 Major inter-individual differences were observed , which could not be attributed to differences in cytochrome P450-medi ated bioactivation rates. This suggests that the variation in individu al susceptibility to BrB may be related to interindividual differences in the activity of de-activating (metabolic) pathways. 5 The study of the background of these interindividual differences may contribute to a more complete understanding of the factors ruling sensitivity to Br B or related chemicals.