Limited PCB antagonism of TCDD-induced malformations in mice

Abstract

C57BL/6N mice, used to model induction of cleft palate and kidney malformations in offspring following maternal treatment with TCDD, were dosed on gestation day (gd) 9 with 2,2', 4,4', 5,5'-hexachlorobiphenyl (HCB) (62.5, 125, 250, 500, 1000 mg kg ) and/or gd 10 with 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) (15 or 18 μg kg ) to investigate the potential protective effects of HCB against TCDD-induced teratogenicity. Maternal body weight gain was increased by combinations of 15 μg TCDD kg and 125–500 mg HCB kg and decreased at doses of 15 μg TCDD kg + 1000 HCB mg kg . At the doses used in this study, there was no effect of either compound on number of live or dead offspring. Fetal body weight was slightly decreased in all groups dosed with ≥ 250 mg HCB kg . HCB did not induce cleft palate at a dose of 1000 mg kg , but did induce increases in hydronephrosis and hydroureter at 500 and 1000 mg kg . Combinations of HCB and TCDD decreased the incidence of cleft palate induced by TCDD alone, but only at doses of 15 μg TCDD kg combined with 125–500 mg HCB kg . The antagonism of hydronephrosis (incidence and severity) appeared over a narrower dose range (15 μg TCDD kg + 500 mg HCB kg ). HCB induced increases (3-fold) in ethoxyresorufin-O-deethylase (EROD) activity at doses of 500 and 1000 mg kg , suggesting that the limited antagonism of TCDD teratogenicity by HCB could be under the control of the Ah-receptor.