TY - JOUR
AU - Bender, Wanda
AB - 17β-estradiol (E2), estrone and diethylstilbestrol (DES) had noeffect on nuclear and nucleolar RNA synthesis in vitro.However, after reacting with dimethyldioxirane (DMDO), a versatileepoxide-forming oxidant, these estrogens were able to inhibit and in adose-dependent manner nuclear and nucleolar RNA synthesis invitro. It was also found that the time required for the maximalactivation of these chemicals by DMDO varied: estrone, 10 min; E2, 30min; DES, 60 min. Tamoxifen (TAM) was also able to inhibit nuclear and nucleolarRNA synthesis in a dose-dependent manner, but the mechanism of this inhibitionwas more complex. Control experiments clearly indicated, unlike E2,estrone and DES, TAM per se was able to directly inhibit RNAsynthesis in vitro. TAM after activation by DMDO was able tofurther inhibit RNA synthesis contributing part of the total observedinhibition. These data show for the first time that E2, estrone, DESand TAM can be activated by DMDO and possibly to epoxides. We propose thatepoxidation of E2 and estrone may be the underlying mechanism ofcarcinogenesis for these estrogens in vivo.
TI - Activation of 17β-estradiol and estrone by dimethyldioxirane and inhibition of rat liver nuclear and nucleolar RNA synthesis in vitro
JO - Carcinogenesis
DO - 10.1093/carcin/17.9.1957
DA - 1996-09-01
UR - https://www.deepdyve.com/lp/oxford-university-press/activation-of-17-estradiol-and-estrone-by-dimethyldioxirane-and-BTBa4v0e5Q
SP - 1957
EP - 1961
VL - 17
IS - 9
DP - DeepDyve
ER -