Sister chromatid exchanges and cell division delays induced by diethylstilbestrol, estradiol, and estriol in human lymphocytes.
It had been found previously that exposure of human lymphocytes in vitro to diethylstilbestrol (DES), a synthetic estrogen and known human carcinogen, led to the induction of sister chromatid exchanges. More sister chromatid exchanges were induced in cells from pregnant women than from men. To see if the effects of DES could be induced by other estrogens, lymphocytes from a man and a pregnant woman were treated in vitro with the natural estrogens estradiol and estriol. These did not induce sister chromatid exchanges. To see if the presence of exogenous female hormones might be responsible for the increase in DES-induced sister chromatid exchanges seen in cells from pregnant women, lymphocytes from a man and a pregnant woman were also treated in vitro simultaneously with DES, estradiol, estriol, and progesterone. Treatments with these exogenous hormones did not alter the number of DES-induced sister chromatid exchanges. Our previous studies showed that DES also inhibits in vitro proliferation of lymphocytes. The results reported here show that estradiol also strongly inhibits this proliferation but that estriol is only a weak inhibitor. The cause of delayed cell proliferation induced by DES and estradiol was 2-fold: some of the cells were delayed in phytohemagglutinin-mediated blast cell transformation but, additionally, most cells had a prolonged cell cycle because of an extended G2 phase. These studies also showed that DES, but not estradiol or estriol, induced a low level of polyploidy in human lymphocytes.
D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D003434:Crossing Over, Genetic / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D004054:Diethylstilbestrol / Q000633:toxicity*; D004958:Estradiol / Q000633:toxicity*; D004964:Estriol / Q000633:toxicity*; D005260:Female; D006801:Humans; D007399:Interphase / Q000187:drug effects; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008677:Metaphase / Q000187:drug effects; D011247:Pregnancy; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D004958:Estradiol; D004054:Diethylstilbestrol; D004964:Estriol