DIFFERENTIAL INDUCTION OF GST SUBUNITS BY 3-MC AND BHA

拟议研究的具体目标是：(1)确定 异源化合物丁基羟基苯甲醚和3-甲基胆菲 差异调控Yb亚基分离基因的表达 女性肝脏解毒酶谷胱甘肽S转移酶的研究 以及(2)确定协同作用的机制 谷胱甘肽S转移酶Ya亚基结合后的表达 丁基羟基苯甲醚和3-甲基胆蒽对大鼠的治疗作用。 我们实验室的实验结果表明，两者的量都 谷胱甘肽S转移酶的活性和特异性亚基的数量 通过用这些异源物质治疗大鼠而显著改变 化合物，单独的或组合的。这些结果使我们得出了 假设，对于Yb亚基，每个化合物都专门调节 该亚基的不同形式的表达；对于Ya亚基， 要么每个化合物激活两个或更多单独的Ya基因，要么 化合物共同作用导致一个Ya基因的过度表达。这个 本提案中描述的实验旨在测试这两个方面 假设。除了我的公司现有的人员和资源 新成立的实验室、工作人员和可用的设备 分子生物学研究实验室将用于完成所述的 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.