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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。但其确切的致癌机理仍需进一步研究
OBJECTIVE: To establish a method for the determination of 8-hydroxy-2’-deoxyguanosine (OH8dG) by high pressure liquid chromatography. To study the oxidative damage of DNA to acrylonitrile (AN) and to investigate the carcinogenic mechanism of acrylonitrile. METHODS: Rat liver was used to prepare OH8dG by Ames enzymatic method. The content of OH8dG in DNA was detected by HPLC-ECD. Results: Low dosage of acrylonitrile had no significant effect on the production of reactive oxygen species and OH8dG. With the increase of acrylonitrile dosage, the formation of OH8dG increased. At 80 mgAN / kg, the content of OH8dG was about 6 times that of the control group. CONCLUSIONS: After biotransformation of acrylonitrile by the liver, reactive oxygen species (ROS) can be produced. Hydroxyl radical can hydroxylation of the sixth position of deoxyguanosine in the liver DNA to form OH8dG, while OH8dG can cause G: C → T: A transversion, causing mutation. This pathway may be an important mechanism of chemical carcinogenesis of acrylonitrile. However, its exact mechanism of carcinogenesis still needs further study