SUPPRESSION OF CYTOCHROME-P450 CYP2F2 MESSENGER-RNA LEVELS IN MICE BYTHE PEROXISOME PROLIFERATOR DIETHYLHEXYLPHTHALATE

Exposure to peroxisome proliferators, which are extensively used, caus es a number of pleiotrophic effects, Prolonged exposure to the peroxis ome 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 differentia l 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 i n mouse liver following DEHP treatment. A smaller Cyp2f2 mRNA transcri pt was also detected in kidney and these transcript levels were also s uppressed but to a lesser extent than that in the liver, The response to DEHP in mouse liver is both dose and time dependent.