【作者】 刘昕；

【导师】 戴乾圜；

【作者基本信息】 北京工业大学 ， 环境科学， 2000， 硕士

【摘要】 双区理论是探讨有机致癌活性关系领域的一项重大突破，目前双区理论正受到国内外的广泛关注。本论文的目的就是根据双区理论的推导进行实验研究，以期为双区理论提供实验旁证，探讨致癌机理。 动物实验及流行病调查证明，雌二醇和己烯雌酚均具有致癌性。戴乾圜教授根据其致癌机理的双区理论推论：雌激素是由于引发DNA互补碱基共价交联而启动致癌作用。借DNA碱洗脱法首次证明雌二醇和己烯雌酚经代谢活化均剂量相关的引起DNA-蛋白质间和DNA股间交联，而非致癌的胆固醇和芘均不能引起交联。已知雌激素与多环芳烃污染具有彼此增强的致癌作用，不能诱发交联的非致癌剂芘与雌二醇共同培育，则总交联率和DNA股间交联率分别达到雌二醇单独作用时的四倍及三倍，表明雌二醇不仅诱发芘生成双自由基，而芘又反过来促进雌二醇双基的更多形成。 双区理论同时预测物理致癌机理也是源于物理因素引发DNA互补碱基共价交联，用DNA碱洗脱法，以致癌的石棉和不致癌的玻璃纤维作比较，首次证明石棉能剂量相关的引起DNA-蛋白质间和DNA股间交联，而非致癌的玻璃纤维不能引起交联，表明石棉能够诱发自由基与DNA发生交联，从而引发癌变。 上述实验结果符合双区理论的推导，提示致癌剂产生的DNA交联损伤在致癌过程中将产生一定的作用。更多还原

【Abstract】 Di-region theory is a great breakthrough in the research field of the relationship between carcinogens and their structures, with wide attention domestically and abroad. In order to provide the experimental evidence and to explore the mechanism of carcinogenesis, we designed a modified alkaline elution experiment to examine the DNA cross-link ability of some selected procarcinogens: 17- 13 -Estradiol, Diethylstibestrol(DES) and the jointaction of 17- f3 -Estradiol and Pyrene, according to di-region theory.Estradiol and Diethylstilbestrol (DES) in estrogens are all carcinogens based upon animal experiments and epidemiological investigation. It is concluded from the di-region theory, a mechanism conception put forward by Professor Di Qianhuan, that the carcinogenesis of estrogens is switched on by the covalent cross-link between complementary DNA bases induced by them. We verified for the first time through DNA alkaline elution method that both estradiol and diethylstilbestrol can cause covalent cross-link between DNA-protein and DNA interstrands after metabolic activation with dosage correlation, but neither cholesterol nor pyrene which are non-carcinogens can lead to these sorts of cross-link in the same condition.It is known that there is a synergetic effect between estrogen and pollution of polycyclic aromatic hydrocarbons. Although non-carcinogenic pyrene alone cannot induce cross-link, its addition with equal molar quantity to estradiol culture causes synergically that the total and DNA interstrand cross-link ratio are respectively four and three times increasing than those in the cultivation with estradiol only. It would be shown that not only estradiol set off the formation of pyrene bi-radicals, but also the pyrene radicals arouse conversely the production of estradiol bi-radicals.The discovery of di-region theory predicts the mechanism of physical matters is also concerned with DNA cross-link. The DNA alkaline elution method showed that carcinogen asbestos produced certain degree of DNA cross-link with dosage correlation. However, the analogic non-carcinogen glassfiber did not show the ability of cross-link under the same condition.Liuxin (Major: Environmental Science)Directed by Di Qianhuan更多还原