Suppression of cytochrome P450 Cyp2f2 mRNA levels in mice by the peroxisome proliferator diethylhexylphthalate

Abstract

Exposure to peroxisome proliferators, which are extensively used, causes a number of pleiotrophic effects. Prolonged exposure to the peroxisome proliferator, DEHP, causes hepatic hyperplasia and liver tumors in rats and mice. This exposure can also induce a number of enzymes. To identify additional genes that are regulated by DEHP, mRNA differential display was used. One of the genes affected is cytochrome 450 Cyp2f2, a naphthalene hydroxylase. Using northern analysis, RNase protection assay, and RT-PCR, we show that the Cyp2f2 mRNA levels are decreased in mouse liver following DEHP treatment. A smaller Cyp2f2 mRNA transcript was also detected in kidney and these transcript levels were also suppressed but to a lesser extent than that in the liver. The response to DEHP in mouse liver is both dose and time dependent.