Role of isozyme-specific inhibition of cytochrome P450IIB1 activity in m-xylene-induced alterations in rat pulmonary benzo(a)pyrene metabolism

Abstract

1. m-Xylene (1 g/kg, i.p., 1 h) increased formation of benzo(a)pyrene (BP) mutagenic bay region diols, BP-7,8-diol (66%) and BP-9,10-diol (56%) by rat pulmonary microsomal preparations, while formation of individual BP phenols and quinones was unaltered.

2. m-Xylene administration produced a decrease in cytochrome P450IIB1 activity as measured by pentoxy- and benzyloxy-resorufin O-dealkylation (PROD, BROD), while cytochrome P450IA1 activity, expressed as ethoxyresorufin O-dealkylation (EROD), was unaltered.

3. Pulmonary microsomal epoxide hydrolase activity was also unaltered by m-xylene.

4. In summary, m-xylene alters the relative contribution of P-450 isozymes to BP metabolism resulting in inhibition of BP detoxication and increased production of toxic metabolites.