TY - JOUR
T1 - Depurinating estrogen-DNA adducts in the etiology and prevention of breast and other human cancers
AU - Cavalieri, Ercole L.
AU - Rogan, Eleanor G.
PY - 2010
Y1 - 2010
N2 - Experiments on estrogen metabolism, formation of DNA adducts, mutagenicity, cell transformation and carcinogenicity have led to and supported the hypothesis that the reaction of specific estrogen metabolites, mostly the electrophilic catechol estrogen-3,4-quinones, with DNA can generate the critical mutations to initiate breast and other human cancers. Analysis of depurinating estrogen-DNA adducts in urine demonstrates that women at high risk of, or with breast cancer, have high levels of the adducts, indicating a critical role for adduct formation in breast cancer initiation. Men with prostate cancer or non-Hodgkin lymphoma also have high levels of estrogen-DNA adducts. This knowledge of the first step in cancer initiation suggests the use of specific antioxidants that can block formation of the adducts by chemical and biochemical mechanisms. Two antioxidants, N-acetylcysteine and resveratrol, are prime candidates to prevent breast and other human cancers because in various in vitro and in vivo experiments, they reduce the formation of estrogen-DNA adducts.
AB - Experiments on estrogen metabolism, formation of DNA adducts, mutagenicity, cell transformation and carcinogenicity have led to and supported the hypothesis that the reaction of specific estrogen metabolites, mostly the electrophilic catechol estrogen-3,4-quinones, with DNA can generate the critical mutations to initiate breast and other human cancers. Analysis of depurinating estrogen-DNA adducts in urine demonstrates that women at high risk of, or with breast cancer, have high levels of the adducts, indicating a critical role for adduct formation in breast cancer initiation. Men with prostate cancer or non-Hodgkin lymphoma also have high levels of estrogen-DNA adducts. This knowledge of the first step in cancer initiation suggests the use of specific antioxidants that can block formation of the adducts by chemical and biochemical mechanisms. Two antioxidants, N-acetylcysteine and resveratrol, are prime candidates to prevent breast and other human cancers because in various in vitro and in vivo experiments, they reduce the formation of estrogen-DNA adducts.
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U2 - 10.2217/fon.09.137
DO - 10.2217/fon.09.137
M3 - Review article
C2 - 20021210
AN - SCOPUS:75149174413
SN - 1479-6694
VL - 6
SP - 75
EP - 91
JO - Future Oncology
JF - Future Oncology
IS - 1
ER -