Pulmonary Cyp1A1 and CYP1A2 levels and activities in adult male and female offspring 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-day-old male and female, and 120-day-old male offspring of pregnant rats treated with five weekly 0.1 microg/kg doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during gestation and lactation were compared with those in age-matched offspring of untreated dams. The CYP1A1-preferential activity, ethoxyresorufin 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 was undetectable in 120-day-old offspring of untreated or treated dams. CYP1A2 activity, as measured by the bioactivation of 2-amino-3,4-dimethylimidazo[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 dams; it was detected in 40-day-old offspring of treated dams, at a level that was higher in females than in males. The results show that gestational and lactational exposure to TCDD causes long-lasting and gender-preferential induction of CYP1A1 as well as CYPIA2 in the lungs of rat offspring.
Iba
M M
MM
Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ 08854, USA. iba@eohsi.rutgers.edu
Fung
J
J
D000818:Animals; D001711:Biotransformation; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D007774:Lactation / Q000187:drug effects*; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D011804:Quinolines / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000633:toxicity*
D000072317:Polychlorinated Dibenzodioxins; D011804:Quinolines; D012333:RNA, Messenger; D013723:Teratogens; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; C036989:2-amino-3,4-dimethylimidazo(4,5-f)quinoline