You are here:
2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) DISTRIBUTION AND CYTOCHROME P4501A INDUCTION IN YOUNG ADULT AND SENESCENT MALE MICE
Citation:
Pegram, R., J. Diliberto, T. Moore, P. Gao, AND L. Birnbaum. 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) DISTRIBUTION AND CYTOCHROME P4501A INDUCTION IN YOUNG ADULT AND SENESCENT MALE MICE. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/304, 1995.
Description:
While the developmental toxicology of TCDD and its congeners has received considerable attention, the impact of advanced age on the biochemical effects and the pharmacokinetics of dioxins remains largely undetermined. n the present investigation, TCDD tissue distribution and cytochrome P4501A (CYP1A) induction were characterized in male C57BL/6N mice aged 10 weeks and 28 months at 7 days after administration of single oral [3H]-TCDD doses ranging from 0.015 to 15 ug/kg body wt. eterminations of hepatic marker enzyme activities for CYP1A1 and 1A2 indicated that the dose response curves for CYP1A1 induction by TCDD were nearly identical for the two age groups, but the CYP1A2 induction response was greater in old mice. fter receiving the 15 ug/kg dose, an increase (-35%) in relative liver weight was observed 7 days after dosing in the 10 wk mice, but not in the aged mice, and the hepatic concentration of TCDD was -25% greater in young than old mice. o age difference was found in hepatic nuclear concentrations of TCDD. ose-dependent increase in liver:fat tissue concentration ratios was noted at both ages, and adipose tissue and blood concentrations of TCDD did not vary significantly with age. n old mice however, TCDD concentrations in skin, kidney and muscle were all approximately twice those of young mice at the 15 ug/kg dose. hese results suggest that advanced age has differential effects on Ah receptor mediated enzyme induction, while increased TCDD concentrations in certain tissues may have toxicological implications for older animals.