CELL-CYCLE DISTURBANCE IN RELATION TO MICRONUCLEUS FORMATION INDUCED BY THE CARCINOGENIC ESTROGEN DIETHYLSTILBESTROL

In addition to its tumor-promoting activity in hormone-receptive tissu e, the carcinogenic estrogen diethylstilbestrol (DES) has been found t o induce cell transformation, aneuploidy and micronucleus formation in mammalian cells. The majority of these micronuclei contained whole ch romosomes and were formed during mitosis. Here a possible relationship between a disturbance in cell cycle progression and micronucleus form ation is investigated by exposing Syrian hamster embryo (SHE) cells to DES. Continuous bromodeoxyuridine labeling followed by bivariate Hoec hst 33258/ethidium bromide flow cytometry was employed for analysis of cell cycle transit and related to the time course of micronucleus for mation. Treatment of SHE cells with DES resulted in delayed and impair ed cell activation (exit from the G0/G1 phase), impaired S-phase trans it and, mainly, G2-phase traverse. Cells forming micronuclei, on the o ther hand, were predominantly in G2 phase during DES treatment. These results suggest that impairment of S and G2 transit may involve a proc ess ultimately leading to micronucleus formation.