A systematic gene expression screen of Caenorhabditis elegans cytochrome P450 genes reveals CYP35 as strongly xenobiotic inducible

The soil nematode Caenorhabditis elegans is one of the simplest animals hav ing the status of a laboratory model. Its genome contains 80 cytochrome P45 0 genes (CYP). In order to study CYP gene expression in C. elegans mixed st ages and synchronized hermaphrodites were exposed to IS known xenobiotic cy tochrome P450 inducers. Messenger RNA expression was detected by DNA arrays and semiquantitative RTPCR. Using subfamily-specific primers, a pooled set of exon-rich CYP fragments could be amplified. In this way it was possible to systematically check the influence of different inducers on CYP express ion at the same time. The well-known CYP1A inducers beta -naphthoflavone, P CB52, and lansoprazol were the most active and in particular they strongly induced almost all CYP35 isoforms. A few number of further CYP forms were f ound to be inducible by other xenobiotics like phenobarbital, atrazine, and clofibrate. In addition, a transgenic C. elegans line expressing CYP under control of the CYP35A2 promoter showed a strong induction of the fusion by beta -naphthoflavone in the intestine. (C) 2001 Academic Press.