利用生物标记物OH^8dG研究丙烯腈对DNA的氧化损伤

STUDIES ON OXIDATIVE DNA DAMAGE CAUSED BY ANA CRYLONITRILE WITH OH8dG AS BIOMARKER

目的：建立高压液相检测８－羟基－２＇－脱氧鸟苷（ＯＨ８ｄＧ）的方法；研究丙烯腈（ＡＮ）对ＤＮＡ的氧化性损伤；探讨丙烯腈的致癌机理。方法：以大鼠肝为材料，用Ａｍｅｓ酶解法制备ＯＨ８ｄＧ，用ＨＰＬＣ－ＥＣＤ检测ＤＮＡ中ＯＨ８ｄＧ含量。结果：小剂量丙烯腈对活性氧自由基及ＯＨ８ｄＧ的产生无明显影响，随着丙烯腈剂量的增加，ＯＨ８ｄＧ形成增加。８０ｍｇＡＮ／ｋｇ时，ＯＨ８ｄＧ的含量约为对照组的６倍。结论：丙烯腈经肝脏生物转化后，可产生活性氧自由基（ＲＯＳ），通过羟自由基使肝ＤＮＡ中脱氧鸟苷第６位羟化，形成ＯＨ８ｄＧ，而ＯＨ８ｄＧ可引起Ｇ∶Ｃ→Ｔ∶Ａ颠换，从而引起突变。这一途径可能是丙烯腈化学致癌的重要机制。

Objective:Established the HPLC method to test OH8dG, studied the oxidative damage of DNA caused by acrylonitrile (AN) and probed the mechanism of carcinogensis of AN Methods: Made use of the rat's livers as experiment material to prepare the OH8dG with Ames method We also measured the content of OH8dG in DNA with HPLCECD method Results: Low dose of AN hasn't any obvious effect on reactive oxygen radicals and OH8dG The formation of OH8dG increases following the increased dose of AN When the amount of AN is 80mg/kg weight, the amount of OH8dG in experiment group is about six times of that of the control group Conclusion:AN produces ROS after being Biotransformed in liver, Hydroxyl free radicals mediate OH8dG formation from deoxyguanosine Formation of OH8dG in DNA induces G…C→T∶A transversion and then produces mutation This may be the important mechanism which AN induces chemical carcinogensis