Extensive evidence exists that the reaction of
estrogen metabolites with
DNA produces depurinating adducts that, in turn, induce mutations and cellular transformation. While it is clear that these
estrogen metabolites result in a neoplastic phenotype in vitro, further evidence supporting the link between
estrogen-
DNA adduct formation and its role in
neoplasia induction in vivo would strengthen the evidence for a genotoxic mechanism.
Diethylstilbestrol (DES), an
estrogen analogue known to increase the risk of
breast cancer in women exposed in utero, is hypothesized to induce
neoplasia through a similar genotoxic mechanism. Cultured MCF-10F human breast epithelial cells were treated with DES at varying concentrations and for various times to determine whether the addition of DES to MCF-10F cells resulted in the formation of depurinating adducts. This is the first demonstration of the formation of DES-
DNA adducts in human breast cells. A dose-dependent increase in DES-
DNA adducts was observed. Demonstrating that treatment of MCF-10F cells with DES, a known human
carcinogen, yields depurinating adducts provides further support for the involvement of these adducts in the induction of breast
neoplasia. Previous studies have demonstrated the ability of
antioxidants such as
resveratrol to prevent the formation of
estrogen-
DNA adducts, thus preventing a key carcinogenic event. In this study, when MCF-10F cells were treated with a combination of
resveratrol and DES, a dose-dependent reduction in the level of DES-
DNA adducts was also observed.