Differences in Induction of Three P450 Isozymes by Piperonyl Butoxide, Sesamex, Safrole, and Isosafrole

The induction of the P450 isozymes 1a-1, 1a-2, and 2b-10 by four methylenedioxyphenyl (MDP) compounds, safrole (SAF), isosafrole (ISO), piperonyl butoxide (PBO), and sesamex (SES), and by the nonmethylenedioxyphenyl analog of SAF, allyl benzene (AB), was studied using male C57BL/6N mice. P450 1a-1 was not detected in control animals, and was induced by SES and PBO, with SES inducing more 1a-1 protein than PBO. P450 1a-2 mRNA was detected in the livers of control animals and was also increased by all MDP compounds (SES > PBO ≅ ISO > SAF), although SAF treatment did not increase 1a-2 protein. P450 2b-10 mRNA and protein, not detected in untreated animals, were also increased by all MDP compounds (PBO > SES ≅ ISO > SAF). AB treatment did not induce detectable levels of 1a-1, 1a-2, or 2b-10, suggesting that, in this series of compounds, the methylenedioxyphenyl moiety is important in induction.