CYP 450 enzyme induction by chronic oral musk xylene in adult and developing rats (vol 111, pg 117, 1999)

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 conce ntrations of 1 mg, 10 mg, 33 mg, 100 mg and 1000 mg MX per 1 kg chow corres ponding to a daily intake of 0.07-0.08 mg MX/kg up to 70-80 mg MX/kg body w eight. Adult male and female rats were MX exposed for a minimum of 10 weeks before mating. Exposure continued throughout pregnancy, birth and lactatio n. 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 thes e enzymes dose dependently in adult and developing rats at PN (postnatal da y) 1 and 14. The lowest effective maternal dose was 2-3 mg MX/kg/day. Weste rn 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 differe ntial sensitivity to MX in development. (C) 2000 Elsevier Science Ireland L td. All rights reserved.