出版社:Korean Society of Environmental Health and Toxicology
摘要:Glutathione- S - transferases (GSTs) detoxifty electrophilic xenobiotics and reactive metabolites. Recently benzene - fused heterocycles have been shown to increase the total amount of hepatic GSTs in rats. Primarily this study aimed to determine the induction of GSTs by benzoazoles (BAs) including benzoxazole (BX),2-methylbenzoxazole (M - BX), 2,5-dimethyl benzoxazole (D BX),benzothiazole (BT),aminobenzothiazole (A-BT) and 2- mercaptobenzothiazole (M-BT) in rats. Hepatic cytosol and poly (A)+ mRNA were prepared from rats after oral administration of BX,BT,M-BX. D-BX,A-BT and M- BT for 5 consecutive days at doses of 1mmol/kg. Western immunoblot and northern blot analysis were conducted with rabbit anti-GST Ya,Yb。 Yb. Ye antibodies and cDNA probes containing ≈500bps in the specific coding regions of Ya,Yb,Yb,,Yc and Ye, respectively. Al BAs increased the amount of enzymes and mRNA levels of GSTs. BT was the most effective inducer of GSTs among the compounds examined in this study. Although A-BT and MBT. the derivatives of BT. induced GSTs. these chemicals had lesser effect on induction of GSTs than BT,The derivatives of BX also induced less GSTs than the parent compound and the addition of methyl group to the benzene ring of BX reduced the induction of GSTs. BAs had better inductive effects on the class a (Ya, Yc) than class μ GSTs(Yb. Ybz)。 BAs enhanced mRNA levels of GSTs in parallel with the protein levels. These results indicate that 1) most of BAs induced various isozymes of GSTs,2) the induction of GSTs appears to be correlated with the chemical structure of the derivatives,and 3) the expression of GST by BAs is presumably under the transcrip tional regulation.
关键词:glutathione -S- -transferases. benzsazoles. rat