ACTIVATION OF 17-BETA-ESTRADIOL AND ESTRONE BY DIMETHYLDIOXIRANE AND INHIBITION OF RAT-LIVER NUCLEAR AND NUCLEOLAR RNA-SYNTHESIS IN-VITRO

17 beta-estradiol (E(2)), estrone and diethylstilbestrol (DES) had no effect on nuclear and nucleolar RNA synthesis in vitro, However, after reacting with dimethyldioxirane (DMDO), a versatile epoxide-forming o xidant, these estrogens were able to inhibit and in a dose-dependent m anner nuclear and nucleolar RNA synthesis in vitro, It was also found that the time required for the maximal activation of these chemicals b y DMDO varied: estrone, 10 min; E(2), 30 min; DES, 60 min, Tamoxifen ( TAM) was also able to inhibit nuclear and nucleolar RNA synthesis in a dose-dependent manner, but the mechanism of this inhibition was more complex, Control experiments clearly indicated, unlike E(2), estrone a nd DES, TAM per se was able to directly inhibit RNA synthesis in vitro , TAM after activation by DMDO was able to further inhibit RNA synthes is contributing part of the total observed inhibition, These data show for the first time that E(2), estrone, DES and TAM can be activated b y DMDO and possibly to epoxides, We propose that epoxidation of E(2) a nd estrone may be the underlying mechanism of carcinogenesis for these estrogens in vivo.