Endogenous
estrogens become
carcinogens when excessive
catechol estrogen quinone metabolites are formed. Specifically, the
catechol estrogen-3,4-quinones can react with
DNA to produce a large amount of specific depurinating
estrogen-
DNA adducts, formed at the N-3 of Ade and N-7 of Gua. Loss of these adducts leaves apurinic sites in the
DNA, which can generate subsequent
cancer-initiating mutations. Unbalanced
estrogen metabolism yields excessive
catechol estrogen-3,4-quinones, increasing formation of the depurinating
estrogen-
DNA adducts and the risk of initiating
cancer. Evidence for this mechanism of
cancer initiation comes from studies in vitro, in cell culture, in animal models and in human subjects. High levels of
estrogen-
DNA adducts have been observed in women with breast, ovarian or
thyroid cancer, and in men with
prostate cancer or
non-Hodgkin lymphoma. Observation of high levels of depurinating
estrogen-
DNA adducts in high risk women before the presence of
breast cancer indicates that adduct formation is a critical factor in
breast cancer initiation. Two dietary supplements,
N-acetylcysteine and
resveratrol,
complement each other in reducing formation of
catechol estrogen-3,4-quinones and inhibiting formation of
estrogen-
DNA adducts in cultured human and mouse breast epithelial cells. They also inhibit malignant transformation of these epithelial cells. In addition, formation of adducts was reduced in women who followed a Healthy Breast Protocol that includes
N-acetylcysteine and
resveratrol. Blocking initiation of
cancer prevents promotion, progression and development of the disease. These results suggest that reducing formation of depurinating
estrogen-
DNA adducts can reduce the risk of developing a variety of types of human
cancer.