Induction of the estrogen effect-switching phenomenon by ethanol and its correction.

Female rats (aged three months at the start of the study) were kept for four months on drinking water (group 1) or 5% ethanol. Rats drinking ethanol were additionally divided into six groups (groups 2-7). During the next two months of the experiment, animals of group 2 continued to drink only ethanol, while rats of group 3 additionally received N-acetylcysteine, those of group 4 received ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E), those of group 5 received melatonin, those of group 6 received carnosine, and those of group 7 swam in the so-called training regime for five days a week. All animals underwent bilateral ovariectomy 2.5 weeks before experiments ended, and were given daily i.m. estradiol (2 microg) during the 11 days before the last experimental day. After treatments, blood estradiol and cholesterol levels were measured, along with progesterone receptor levels, peroxidase activity, the index of proliferation, the proportions of cells in the S and G2/M phases, the thickness of the endometrium, and the extent of DNA damage (using the "comet" technique) in uterine tissue. Liver estradiol 2-hydroxylase activity was also measured. The results led to the conclusion that drinking of 5% ethanol in combination with administration of estrogens was accompanied by induction of genotoxic (G) changes in the uterus and that this was prevented by administration of N-acetylcysteine and melatonin. The combination of vitamins C and E increased some of the manifestations of the hormonal (H) effect of estrogens (uterine weight and induction of progesterone receptors), but weakened others (the index of proliferation). As a result, the combination of N-acetylcysteine and optimum doses of ascorbic acid and alpha-tocopherol can be recommended for preventing the estrogen effect-switching phenomenon (increases in the G component on the background of weakening of the H component), which is seen particularly in patients consuming excessive amounts of alcohol, increasing the risk that the genotoxic version of hormonal cancerogenesis will develop.