Polymorphic ochratoxin A hydroxylation in rat strains phenotyped as poor and extensive metabolizers of debrisoquine

Abstract

1. Dark agouti (DA) and Lewis rat strains, which show a genetic polymorphism for debrisoquine-4-hydroxylation, were treated either with a single dose of ochratoxin A (OA) or for 8 weeks with 5 doses per week. Levels of OA and its 4-hydroxy metabolite (4-hydroxy-OA) excreted in urine were determined.

2. At all doses, the metabolic ratio of OA: 4-hydroxy-OA was two to five times greater in DA than in Lewis rats, as was the metabolic ratio of debrisoquine: 4-hydroxy-debrisoquine. These results are consistent with our previous findings in vitro that hepatic and renal OA 4-hydroxylase activity is three to four times lower in DA than in Lewis rats. These data give further support to the possible co-segregation of genes regulating OA and debrisoquine 4-hydroxylation.