Effect of gestational and lactational 2,3,7,8 tetrachlorodibenzo-p-dioxin exposure on the level and catalytic activities of hepatic microsomal CYP1A in prepubertal and adult rats

We determined the inducibility, as well as the persistence of the induction , of hepatic microsomal CYP1A1 and CYP1A2 (by western blot analysis), and t heir catalytic activities (as measured by resorufin ether O-dealkylation) i n prepubertal (25-day-old) and adult (120-day-old) offspring of timed-pregn ant Sprague-Dawley rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (T CDD). TCDD treatment was subcutaneous, at a low dose of 0.1 mu g/kg, on ges tational days 7, 14, and 20, and on lactational days 7 and 14. CYP1A1 prote in was induced significantly (23-fold) in prepubertal but nor: in adult off spring of TCDD-exposed dams, whereas ethoxyresorufin O-deethylase (EROD) ac tivity, which is CYP1A1-preferential, was induced less extensively (5-fold) and slightly (1.7-fold) in the prepubertal and adult offspring, respective ly. Benzyloxyresorufin O-debenzylase (BROD) activity, which is CYP2B-prefer ential but has been reported to be catalyzed by CYP1A1, was also induced 5- and 6-fold in prepubertal and adult offspring, respectively, of TCDD-expos ed dams. However, the induced BROD activity was neither inhibited by antibo dy against CYP1A1 nor accompanied by an elevated level of microsomal CYP2B. CYP1A2 was induced slightly only in prepubertal offspring of TCDD-created dams. There was suggestive evidence of enhanced lipid peroxidation in hepat ic microsomes from prepubertal but not adult offspring of TCDD-treated dams . These data showed that in utero plus lactational TCDD exposure effected t ransient induction of hepatic microsomal CYP1A1 but sustained induction of BROD activity, which may be catalyzed by enzymes other than CYP1A or CYP2B. (C) 2000 Elsevier Science Inc.