title: Critical depurinating DNA adducts: Estrogen adducts in the etiology and prevention of cancer and dopamine adducts in the etiology and prevention of Parkinson's disease.
abstract: Endogenous estrogens become carcinogens when dangerous metabolites, the catechol estrogen quinones, are formed. In particular, the catechol estrogen-3,4-quinones can react with DNA to produce an excess of specific depurinating estrogen-DNA adducts. Loss of these adducts leaves apurinic sites in the DNA, generating subsequent cancer-initiating mutations. Unbalanced estrogen metabolism yields excessive catechol estrogen-3,4-quinones, increasing formation of depurinating estrogen-DNA adducts and the risk of initiating cancer. Evidence for this mechanism of cancer initiation comes from various types of studies. High levels of depurinating estrogen-DNA adducts have been observed in women with breast, ovarian or thyroid cancer, as well as 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. Formation of analogous depurinating dopamine-DNA adducts is hypothesized to initiate Parkinson's disease by affecting dopaminergic neurons. 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 cells. In addition, formation of adducts was reduced in women who followed a Healthy Breast Protocol that includes N-acetylcysteine and resveratrol. When initiation of cancer is blocked, promotion, progression and development of the disease cannot occur. These results suggest that reducing formation of depurinating estrogen-DNA adducts can reduce the risk of developing a variety of types of human cancer.
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE.|Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Ercole L
authors.identifier: 0000-0001-7502-0020
authors.initials: EL
authors.lastname: Cavalieri
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE.|Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Eleanor G
authors.initials: EG
authors.lastname: Rogan
authors.affiliation: Department of Environmental, Agricultural and Occupational Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Zahid
mesh_terms: D000818:Animals; D018736:DNA Adducts / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D011687:Purines / Q000378:metabolism
chemical_list: D018736:DNA Adducts; D004967:Estrogens; D011687:Purines; D004298:Dopamine
keywords: catechol estrogen-3,4-quinones; depurinating DNA adducts; dopamine 3,4-quinone