[Metabolic effect of tobacco smoke and "switching" the estrogen effect: mechanism of increased genotoxicity].

Earlier studies demonstrated dynamic changes in the hormonal and genotoxic effects of estrogens and a decrease in estradiol concentrations and/or aromatase (estrogen synthetase) activity in the uterine tissue in rats exposed to tobacco smoke (TS) and in endometrial and breast tumor tissues of female smokers. This study was the first to reveal an elevation in the excretion of 2- and 4-hydroxyestrogens in smoking postmenopausal women receiving estrogen-replacement therapy, an increase in estrogen-2-hydroxylase activity in the breast and endometrial tumors of the smokers, and no signs of higher aneuploidy frequency in the cervicovaginal epithelium of mice exposed to TS + estrogens. Thus, it can be concluded that there are different stages of endocrine and genotoxic effects of a TS + estrogen combination which may be related to the specific mechanisms and types of hormonal carcinogenesis. A combination of estrogens and smoking induces such variants of DNA damage, which are mediated mainly through the metabolism of catecholestrogens/free radical formation and not through increased or incorrect (aneuploidy) proliferation.