However, excess ROS could chemically modify cellular macromolecules including DNA, proteins, carbohydrates, or lipids, thereby disrupting normal physiological functions of these biomolecules [76]. Oxidative metabolism of estrogen produces enough ROS in cells. Estrogen-mediated oxidative DNA damage in mammary gland epithelia includes the induction of 8-oxo-2'-deoxyguanosine, both in vitro and in vivo. The data may explain some of the estrogen-induced pro-oxidant effects previously reported in vivo [77]. In addition, this is the first report indicating that E2 is capable of inducing an increase in sensitivity to oxidative DNA damage through an ER-mediated mechanism [78]. Evidence for a one-electron oxidation of estradiol to its reactive phenoxyl radical intermediate is presented. The phenoxyl radical metabolite abstracts hydrogen from reduced glutathione generating the glutathione thiyl radical [79, 80].
However, excess ROS could chemically modify cellular macromolecules including DNA, proteins, carbohydrates, or lipids, thereby disrupting normal physiological functions of these biomolecules [76]. Oxidative metabolism of estrogen produces enough ROS in cells. Estrogen-mediated oxidative DNA damage in mammary gland epithelia includes the induction of 8-oxo-2'-deoxyguanosine, both in vitro and in vivo. The data may explain some of the estrogen-induced pro-oxidant effects previously reported in vivo [77]. In addition, this is the first report indicating that E2 is capable of inducing an increase in sensitivity to oxidative DNA damage through an ER-mediated mechanism [78]. Evidence for a one-electron oxidation of estradiol to its reactive phenoxyl radical intermediate is presented. The phenoxyl radical metabolite abstracts hydrogen from reduced glutathione generating the glutathione thiyl radical [79, 80].