Abstract
2,3,7,8-tetrachroldibenzo-p-dioxin (TCDD) is one of most persistent and bioaccumulative among the Dioxins, so its chronic toxicity is a great concern. However, it has been reported that TCDD is excreted in urine, although only in small amounts. This report suggests that the mammalians might have a metabolic machinery of TCDD, but it remains unclear for a long time. In this study, we newly found that thyroid hormones (TH) promote urinary excretion of TCDD. We here investigated the effects of TH on the urinary excretion of TCDD and its distribution in various tissues, as well as the mechanism by which TH promote its excretion. In order to trace excretion and tissue distribution levels of TCDD, male ddY mice and C57BL/6J mice were intraperitoneally administrated [3H]-labeled TCDD and measured its radioactivity in the liver, feces, and urine. In both species, ddY and C57BL/6J mice, TH did not significantly change fecal excretion of [3H]TCDD, but significantly increased its urinary excretion with a decrease in its accumulation in the liver, the major organ of TCDD accumulation. Similar experiments were conducted using TH receptor (TR) α-knockout (KO) or TRβKO mice. In TRαKO mice, urinary excretion of [3H]TCDD was enhanced with decreased accumulation in the liver, as in wild-type mice, but such effects were not observed in TRβKO mice. These results suggest that the mice have a machinery for urinary excretion of TCDD which may be regulated by TRβ.
