The role of cytochrome P450 in the metabolism of [13C/14C]Styrene

Abstract

Rat, mouse, and human differences occur for the metabolism of styrene. The greater mouse sensitivity to styrene is believed to be related to a higher production of metabolites that are derived from the intermediate phenylacetaldehyde (PM) or from ring-epoxidation of styrene. In this study, the role of cytochrome P450 in the metabolism of styrene was evaluated. Wild-type (WT) mice, mice devoid of cytochrome P4502El (CYP2E 1-null), and CYP2E 1-null mice pretreated with aminobenzotriazole (ABT) were exposed for 6 hr to a 250-ppm mixture of [13C8]styrene and [14C]styrene via nose-only inhalation. Urine, feces, and expired volatiles were collected for up to 24 hr, and mice were sacrificed for the collection of blood and tissues. A greater excretion of total urinary metabolites and total expired [14C]styrene-equivalents was apparent for null mice compared to WT mice. WT mice, CYP2El-null mice, and ABT-CYP2El-null mice excreted metabolites derived from conjugation of styrene oxide with glutathione (~40% of excreted metabolites). WT mice excreted a slightly higher percentage of metabolites derived from hydrolysis of styrene oxide (28%) and a lower percentage of metabolites derived from PM (17%) compared with null mice (16 and 25%, respectively). These data suggest that CYP2El may not be a major isozyme involved in the in vivo metabolism of styrene to styrene oxide in mice.