DIFFERENTIAL INDUCTION OF GST SUBUNITS BY 3-MC AND BHA

本研究的具体目的是：（1）确定 异生物质丁基羟基茴香醚和3-甲基胆蒽 差异调节Yb亚基的不同基因的表达 女性肝脏解毒酶谷胱甘肽S-转移酶 Sprague-Dawley大鼠;（2）确定协同作用的机制 谷胱甘肽S-转移酶Ya亚单位的表达 用丁基羟基茴香醚和3-甲基胆蒽处理大鼠。 我们实验室的实验结果表明， 谷胱甘肽S-转移酶的活性和特定亚基的量 通过用这些异生物质处理大鼠， 化合物，单独或组合。 这些结果使我们 假设对于Yb亚基，每种化合物特异性调节 该亚基的不同形式的表达;并且，对于Ya亚基， 或者每种化合物激活两个或多个独立的Ya基因，或者 化合物一起作用导致一个Ya基因的过度表达。 的 本提案中描述的实验旨在测试这两种方法 假设 除了我的人力和资源外， 新成立的实验室，现有的工作人员和设备， 分子生物学研究实验室将用于完成所述 目标.

The specific aims of the proposed research are to: (1) determine whether the xenobiotics butylated hydroxyanisole and 3-methylcholanthrene differentially regulate the expression of separate genes for the Yb subunit of the hepatic detoxification enzyme glutathione S-transferase in female Sprague-Dawley rats; and (2) determine the mechanism for the synergisic expression of the glutathione S-transferase Ya subunit after combined treatment of rats with butylated hydroxyanisole and 3-methylcholanthrene. Experimental results in our laboratory have shown that both the amount of activity and the amount of specific subunits for glutathione S-transferase are significantly altered by treatment of rats with these xenobiotic compounds, either singly or in combination. These results led us to hypothesize that, for the Yb subunit, each compound specifically regulate the expression of distinct forms of this subunit; and, for the Ya subunit, either each compound activates two or more separate Ya genes or the compounds act together to cause the over-expression of one Ya gene. The experiments described in this proposal are designed to test both these hypotheses. In addition to the personnel and resources available in my laboratory, the staff and equipment available in the newly established Molecular Biology Research Laboratory will be used to accomplish the stated objectives.