Xenobiotic metabolism and the mechanism(s) of benzene toxicity.

The investigation of the mechanism(s) of benzene toxicity/leukemogenesis over the past 50 years has been contemporaneous with developments in the study of xenobiotic metabolism. Research on the cytochrome P450 (CYP) enzyme system, and related systems in vivo and in vitro, which culminated in the isolation and reconstitution of the many CYPs, established pathways for the study of xenobiotic metabolism and its relationship to the biological activity of many chemicals. The essential role for metabolism of benzene as a precursor to the demonstration of benzene toxicity led to extensive studies of benzene metabolism, many of which will be reviewed here. Benzene toxicity/leukemogenesis, however, is a function of the bone marrow, a site remote from the liver where most benzene metabolism occurs. Studies of benzene metabolism have delineated the array of metabolites which appear to play a role in bone marrow damage, but further studies, both in vivo and in vitro, using appropriate animal models, will be needed to fully understand the impact of benzene and its metabolites on bone marrow function.