title: CYP 450 enzyme induction by chronic oral musk xylene in adult and developing rats.
abstract: Developmental and adult toxicity of musk xylene was studied in Long Evans (LE) rats fed with chow containing musk xylene (MX) in food pellets in concentrations of 1 mg, 10 mg, 33 mg, 100 mg and 1000 mg MX per 1 kg chow corresponding to a daily intake of 0.07-0.08 mg MX/kg up to 70-80 mg MX/kg body weight. Adult male and female rats were MX exposed for a minimum of 10 weeks before mating. Exposure continued throughout pregnancy, birth and lactation. The effects of MX on CYP1A1/1A2 were studied in liver microsomes by EROD (7-ethoxyresorufin-o-deethylase) for CYP1A1 and by MROD (methoxyresorufin-o-demethylase) for CYP1A2 activity and by Western blotting. MX induced these enzymes dose dependently in adult and developing rats at PN (postnatal day) 1 and 14. The lowest effective maternal dose was 2-3 mg MX/kg/day. Western blot data of CYP2B and CYP3A indicated the induction of both P450 enzyme proteins in developing rats at PN 14 at the higher dose of 70-80 mg MX/kg/day. In contrast, upon high MX exposure CYP2B but not CYP3A was found to be induced in adult first generation male and female rats, indicating differential sensitivity to MX in development.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, Switzerland.
authors.forename: R
authors.initials: R
authors.lastname: Suter-Eichenberger
authors.forename: U A
authors.initials: UA
authors.lastname: Boelsterli
authors.forename: M
authors.initials: M
authors.lastname: Conscience-Egli
authors.forename: W
authors.initials: W
authors.lastname: Lichtensteiger
authors.forename: M
authors.initials: M
authors.lastname: Schlumpf
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D008297:Male; D010476:Perfume / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014992:Xylenes / Q000633:toxicity*
chemical_list: D010476:Perfume; D014874:Water Pollutants, Chemical; D014992:Xylenes; C031447:musk xylene; D003577:Cytochrome P-450 Enzyme System