| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Research Abstract |
Sulfate conjugation represents a major pathway in vivo for the biotransformation and/or excretion of xenobiotics or endogenous compounds such as steroid and thyroid hormones, catecholamines, and bile acids. The responsible enzymes, so-called "cytosolic sulfotransferases," catalyze the transfer of a sulfonate group from the active sulfate, 3'-phosphoadenosine 5'-phosphosulfate (PAPS), to a substrate compound containing either a hydroxyl or an amino group. It is generally believed that sulfation may increase the water-solubility of xenobiotic or endogenous compounds and facilitate their removal from the body.
In this project, to investigate whether sulfation, a major Phase II detoxification pathway in vivo, can be employed as a means for the inactivation/disposal of environmental estrogens, recombinant human cytosolic sulfotransferases were prepared and tested for enzymatic activities with bisphenol A, diethylstilbestrol, 4-octylphenol, 4-nonylphenol, and 17 α-ethynylestradiol as substrat
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es. Of the seven recombinant enzymes examined, only SULT1C sulfotransferase #1 showed no activities toward the environmental estrogens tested. Among the other six sulfotransferases, the simple phenol (P)-form phenol sulfotransferase and estrogen sulfotransferase appeared to be considerably more active toward environmental estrogens than the other four sulfotransferases. Metabolic labeling experiments revealed the sulfation of environmental estrogens and the release of their sulfated derivatives by HepG2 human hepatoma cells. Moreover, sulfated environmental estrogens appeared to be incapable of penetrating through the HepG2 cell membrane. The results obtained in this project study showed clearly the occurrence of the sulfation of environmental estrogens. That the sulfated environmental estrogens failed to penetrate through the HepG2 cell membrane may imply sulfation as a useful mechanism for the removal of these hazardous compounds. More studies are warranted in order to fully appreciate the involvement of different sulfotransferases in the inactivation/removal of environmental estrogens in vivo. Less
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