INDUCTION OF THE CYP4A SUBFAMILY BY PERFLUORODECANOIC ACID - THE RAT AND THE GUINEA-PIG AS SUSCEPTIBLE AND NON-SUSCEPTIBLE SPECIES

Male Wistar rats and male Duncan Hartley guinea pigs were treated with one i.p. dose of perfluorodecanoic acid (PFDA) resulting in pronounce d hepatomegaly in the rat but not the guinea pig. PFDA treatment also resulted in a 4-fold induction of lauric acid 12-hydroxylase activity in the rat but not the guinea pig, indicating induction of the CYP4A s ubfamily of isoenzymes. Consistent with this latter conclusion, Wester n blot analysis of rat liver microsomes using an antibody to CYP4A1 an d Northern blot analysis of RNA extracts using a CYP4A1 cDNA probe, re vealed PFDA-dependent induction of the CYP4A subfamily in the rat but not the guinea pig. Taken collectively, our data has demonstrated that PFDA, like other peroxisome proliferators, is also a CYP4A inducer an d conforms to the well-documented species specificity in induction for this class of compound.