Pulmonary CYP1A1 and CYP1A2 levels and activities in adult male and femaleoffspring of rats exposed during gestation and lactation to 2,3,7,8-tetrachlorodibenzo-p-dioxin

The levels and activities of pulmonary microsomal CYP1A1 and CYP1A2 in 40-d ay-old male and female, and 120-day-old male offspring of pregnant rats tre ated with five weekly 0.1 mug/kg doses of 2,3,7,8-tetrachlorodibenzo-p-diox in (TCDD) during gestation and lactation were compared with those in age-ma tched offspring of untreated dams. The CYP1A1-preferential activity, ethoxy resorufin O-deethylase (EROD), was comparably induced 5.3- and 6.4-fold in 40-day-old male and female offspring, respectively, but was not induced in 120-day-old male offspring, of TCDD-treated dams. Similarly, CYP1A1 protein was induced in 40-day-old female or male offspring of untreated dams but w as undetectable in 120-day-old offspring of untreated or treated dams. CYP1 A2 activity, as measured by the bioactivation of 2-amino-3,4-dimethylimidaz o[4,5-f]quinoline (MeIQ) to mutagens in the Ames assay, was elevated 11.1- and 5.5-fold in 40-day-old female and male offspring, respectively, of TCDD -treated dams, but was unaffected by TCDD exposure in 120-day-old offspring . CYP1A2 protein was undetectable in 40-day-old male or female offspring of untreated dams or in 120-day-old male offspring of treated or untreated da ms; it was detected in 40-day-old offspring of treated dams, at a level tha t was higher in females than in males. The results show that gestational an d lactational exposure to TCDD causes long-lasting and gender-preferential induction of CYP1A1 as well as CYP1A2 in the lungs of rat offspring. (C) 20 01 Elsevier Science Inc. All rights reserved.