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雌激素Ames实验显阴性,但动物实验及流行病调查证明雌二醇和已烯雌酚均具致癌性.根据致癌机理的双区理论推论,雌激素也是由于引发DNA互补碱基共价交联而启动致癌作用.借DNA碱洗脱法证明,雌二醇和乙烯雌酚经代谢活化均剂量相关地引起DNA-蛋白质间和DNA股间交联,而非致癌剂胆甾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的增效致癌作用.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股间交联率分别达雌二醇单独存在时的4倍及3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生成.
The estrogen Ames test was negative, but animal experiments and epidemiological investigations demonstrated that both estradiol and diethylstilbestrol are carcinogenic. According to the two-region theory of the carcinogenic mechanism, estrogen also initiates carcinogenesis due to the covalent cross-linking of complementary bases. By DNA alkaline elution method, it was demonstrated that the metabolic activation of estradiol and diethylstilbestrol caused DNA-protein and DNA strand cross-linking in a dose-dependent manner, while the non-carcinogenic agents cholesterol and gallium could not cause cross-linking. It is known that estrogen and polycyclic aromatic hydrocarbons have synergistic carcinogenic effects with each other. If the non-carcinogenic agent, cross-linked non-cancer agent, is not co-cultured with estradiol, the total cross-linking rate and cross-linking ratio between DNA strands are 4 and 3 times that of estradiol alone, indicating that estradiol not only induces cockroach The formation of diradicals, which in turn promotes more formation of estradiol diradicals.