REGULATION OF CYTOCHROME-P-450 ISOZYMES CYP1A1, CYP1A2 AND CYP2B10 BY3 BENZODIOXOLE COMPOUNDS

Three benzodioxole (ED) compounds were used to investigate the structu ral requirement for regulation of the cytochrome P450 isozymes, CYP1A1 , CYP1A2 and CYP2B10, in mouse liver. Male mice (C57BL/6) were treated intraperitoneally for 3 days with 5-t-butyl-1,3-benzodioxole (t-BBD), 5-n-butyl-1,3-benzodioxole (n-BBD) and 5-(3-oxobutyl)1,3-benzodioxole (o-BBD). t-BBD-induced liver microsomes showed the highest pentoxyres orufin O-dealkylation (PROD) activity, while o-BBD induced microsomes showed slightly higher activity in ethoxyresorufin O-deethylation (ERO D), benzo[a]pyrene hydroxylation (BaP-OH) and acetanilide hydroxylatio n (Acet-OH) assays. In vitro enzyme inhibition assays showed that n-BB D inhibited EROD and Acet-OH activities more than either o-BBD or t-BB D, while PROD activity was evenly inhibited by all three compounds. We stern and northern blots showed that CYP1A1 was not detectably induced by any of the three ED compounds. The levels of CYP1A2 protein and mR NA were increased in all three treated livers. In addition to CYP1A2 i nduction, t-BBD also induced the protein and mRNA for CYP2B10.