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 pronounced 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 subfamily of isoenzymes. Consistent with this latter conclusion, Western blot analysis of rat liver microsomes using an antibody to CYP4A1 and Northern blot analysis of RNA extracts using a CYP4A1 cDNA probe, revealed 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 and conforms to the well-documented species specificity in induction for this class of compound.
Chinje
E
E
Molecular Toxicology Group, School of Biological Sciences, University of Surrey, Guildford, UK.
Kentish
P
P
Jarnot
B
B
George
M
M
Gibson
G
G
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D018076:DNA, Complementary / Q000378:metabolism; D003652:Decanoic Acids / Q000008:administration & dosage / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D005466:Fluorocarbons / Q000008:administration & dosage / Q000633:toxicity*; D006168:Guinea Pigs; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
D018076:DNA, Complementary; D003652:Decanoic Acids; D005466:Fluorocarbons; D007527:Isoenzymes; C036567:perfluorodecanoic acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A