Age-related susceptibility to 3,3 '-iminodipropionitrile-induced olfactorymucosal damage

3,3'-Iminodipropionitrile (IDPN) causes degeneration of the olfactory mucos a (OM) in rodents following systemic exposure. Approximately 30% of the OM degenerates in 21-day- and 10-week-old rats Following a single 200 or 400 m g/kg intraperitoneal (i.p.) dose of IDPN, whereas 100% olfactory mucosal de generation occurred in 21-month-old rats. Age-related changes in the flavin -containing monooxygenases (FMOs,) or heat shock protein 70 (HSP70) were hy pothesized to be responsible for altered olfactory mucosal susceptibility t o IDPN. FMO activity in OM was higher than in liver in rats up to 40 weeks of age. Western blots of OM and liver revealed no change in FMO1 protein; h owever, FMO2, 3, and 5 decreased in olfactory microsomes with age. FMO3 and FMO5 increased in liver microsomes with age. Heat shock protein 70 did not differ between 10-week- and 10-month-old rats in either tissue, The mechan ism underlying the increased susceptibility of older rats is likely a compl ex interaction between the activities of one or more of the enzymes involve d in IDPN metabolism in OM and liver. (C) 1999 Elsevier Science Inc.