Polycyclic aromatic hydrocarbons cause hepatic porphyria in iron-loaded C57BL/10 mice: Comparison of uroporphyrinogen decarboxylase inhibition with induction of alkoxyphenoxazone dealkylations

Abstract Multiple doses of β-naphthoflavone to iron-loaded C57BL/10ScSn mice for 6 weeks caused inhibition of hepatic uroporphyrinogen decarboxylase and a porphyria indistinguishable from that previously only reported for polyhalogenated aromatic chemicals. β-Naphthoflavone and other polycyclic aromatic hydrocarbon inducers of cytochrome P 1 -450-mediated ethoxyphenoxazone deethylation (ethoxyresorufin deethylase), benzo[ a ]pyrene, benz[ a ]anthracene, dibenz[ ah ]anthracene, 3-methylcholanthrene and α-naphthoflavone, also gave porphyria when fed. Isosafrole was inactive but by both methods phenobarbital produced a small but significant inhibition of the decarboxylase. The results demonstrate a toxic action of polycyclic aromatic hydrocarbons which probably does not involve reactive metabolites.