| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
1. The results from the present study show that the effects of 3-methylsulfonyl-2, 2', 4', 5-tetrabromobiphenyl (3-MeSO_2-TetraBrB) on the drug-metabolizing enzymes, CYP2B1 and CYP2B2, are several thousand-fold higher than those of parent TetraBrB or phenobarbital, while the effects of its isomeric 4-MeSO_2-TetraBrB are not.
2. The present results suggest that 3-MeSO_2-TetraBrB plays an important role in the induction of microsomal drug-metabolizing enzymes by TetraBrB.
3. The present findings show that the nine MeSO_2 metabolites of 1, 3-dichlorobenzene (DCB), 1, 2, 4-trichloro-benzene, and tetra-, penta- and hexachlorobiphenyls reduce thyroid hormone levels in rats, suggesting that the metabolites may act as endocrine-disrupters.
4. The present results indicate that increase in the hepatic thyroxine (T_4) glucuronidation after the administration of the eight MeSO_2-polychlorinated biphenyls and 3, 5-dichlorophenyl methyl sulfone possibly because of the induction of both UGT1A1 and UGT1A6 caused the reduction of serum T_4 levels.
5. The difference in total hepatic concentration of MeSO_2 metabolites among DCB-, 2, 2', 4', 5, 5'-pentachlorobiphenyl-(PentaCB-), 2, 2', 3', 4', 5, 6-hexachlorobiphenyl- (HexaCB-) and Kanechlor-500- (KC500-) treated mice, hamsters, tats and guinea pigs was not correlated with that in the decrease in serum total T_4 level.
6. The present findings suggest that the reduction of serum total T_4 level by DCB, HexaCB and KC500 in rats, mice and guines pigs, respectively, would occur at least in part by an increase in T_4 glucuronidation through the induction of hepatic T_4-UDP-glucuronosyltransferase (T_4-UDP-GT), especially UGT1A1 and UGT1A6, while the decrease of serum total T_4 level by PentaCB, TetraBrB and KC500 in mice, hamsters and rats may occur through alternative mechanisms.
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