EFFECTS OF SOME DIETHYLSTILBESTROL METABOLITES AND ANALOGS ON CYTOTOXICITY AND ANEUPLOIDY INDUCTION IN CHINESE-HAMSTER V79 CELLS

We have previously reported the inhibitory effects of diethylstilbestr ol (1) and optically active indenestrol derivatives on microtubule pol ymerization in vitro and their disruptive effect on cytoplasmic microt ubules and cytotoxicity in cultured Chinese hamster V79 cells. In the present study, the cytotoxicities of (+/-)-diethylstilbestrol oxide (2 ), (+)-, (-)- and (+/-)-monomethyl ethers (4) of 2, (+)-dimethyl ether (5) of 2, diethylstilbestrol pinacolone (3), E,E-dienestrol (6), Z,Z- dienestrol (7), meso-hexestrol (8), a mixture of (1R,1'S)4-hydroxyhexe strol and (1R,1'S)4'-hydroxyhexestrol (9), and the 4-hydroxy derivativ e (10) of diethylstilbestrol dimethyl ether were investigated in Chine se hamster V79 cells. The results indicated that the cytotoxic activit y of 10 was the strongest of the compounds tested, although its activi ty was the almost same as that of 1. Moreover, as the activity of (-)- 4 was greater than those of 2 and 1 monomethyl ethers, the effect of 4 on cytotoxic activities was elucidated. In conclusion, the present re sults indicate that the cytotoxic activities of hydroxylated metabolit es are greater than those of each mother compound, although epoxidatio n of 1 leads to a product which can be broken down more readily than t he parent compound.