Inhibition of depurinating estrogen-DNA adduct formation in the prevention of breast and other cancers

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Citations (Scopus)

Abstract

One problem in the efforts to prevent breast cancer has been the lack of recognition that estrogens can initiate cancer by acting as chemical carcinogens and reacting with DNA. Specific metabolites of endogenous estrogens, the catechol estrogen-3,4-quinones, react with DNA to form depurinating estrogen-DNA adducts. Loss of these adducts leaves apurinic sites in the DNA, generating mutations that can lead to the initiation of cancer. If estrogen metabolism becomes unbalanced and generates excessive catechol estrogen-3,4-quinones, formation of depurinating estrogen-DNA adducts and the risk of initiating cancer increase. Inhibiting formation of depurinating estrogen-DNA adducts can, therefore, prevent cancer. Levels of the estrogen-DNA adducts are high in women diagnosed with breast cancer and those at high risk for the disease. The finding that high levels of depurinating estrogen-DNA adducts precede the presence of breast cancer indicates that formation of these adducts is a critical factor in breast cancer initiation. Women with thyroid or ovarian cancer also have high levels of estrogen-DNA adducts, as do men with prostate cancer or non-Hodgkin lymphoma. The findings summarized above and other discoveries led to the recognition that reducing the levels of estrogen-DNA adducts would prevent the initiation of breast and other types of human cancer. We have found that the dietary supplements N-acetylcysteine and resveratrol inhibit estrogen-DNA adduct formation in both cultured human breast cells and in women. These results suggest that these two supplements offer an approach to reduce risk of developing breast and other types of human cancer.

Original languageEnglish (US)
Title of host publicationTrends in Breast Cancer Prevention
PublisherSpringer International Publishing
Pages113-145
Number of pages33
ISBN (Electronic)9783319271354
ISBN (Print)9783319271330
DOIs
StatePublished - Jan 1 2016

Fingerprint

DNA Adducts
Estrogens
Breast Neoplasms
Neoplasms
Breast
DNA
Dietary supplements
Acetylcysteine
Metabolites
Metabolism
Carcinogens
Dietary Supplements
Thyroid Neoplasms
Ovarian Neoplasms
Non-Hodgkin's Lymphoma
Prostatic Neoplasms

Keywords

  • Cancer prevention
  • Catechol estrogen-3,4-quinones
  • Estrogen genotoxicity
  • Estrogen mutagenicity
  • N-acetylcysteine
  • Resveratrol

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Inhibition of depurinating estrogen-DNA adduct formation in the prevention of breast and other cancers. / Cavalieri, Ercole; Rogan, Eleanor G.

Trends in Breast Cancer Prevention. Springer International Publishing, 2016. p. 113-145.

Research output: Chapter in Book/Report/Conference proceedingChapter

Cavalieri, Ercole ; Rogan, Eleanor G. / Inhibition of depurinating estrogen-DNA adduct formation in the prevention of breast and other cancers. Trends in Breast Cancer Prevention. Springer International Publishing, 2016. pp. 113-145
@inbook{543f4d70213d4b90af639dcc651b2696,
title = "Inhibition of depurinating estrogen-DNA adduct formation in the prevention of breast and other cancers",
abstract = "One problem in the efforts to prevent breast cancer has been the lack of recognition that estrogens can initiate cancer by acting as chemical carcinogens and reacting with DNA. Specific metabolites of endogenous estrogens, the catechol estrogen-3,4-quinones, react with DNA to form depurinating estrogen-DNA adducts. Loss of these adducts leaves apurinic sites in the DNA, generating mutations that can lead to the initiation of cancer. If estrogen metabolism becomes unbalanced and generates excessive catechol estrogen-3,4-quinones, formation of depurinating estrogen-DNA adducts and the risk of initiating cancer increase. Inhibiting formation of depurinating estrogen-DNA adducts can, therefore, prevent cancer. Levels of the estrogen-DNA adducts are high in women diagnosed with breast cancer and those at high risk for the disease. The finding that high levels of depurinating estrogen-DNA adducts precede the presence of breast cancer indicates that formation of these adducts is a critical factor in breast cancer initiation. Women with thyroid or ovarian cancer also have high levels of estrogen-DNA adducts, as do men with prostate cancer or non-Hodgkin lymphoma. The findings summarized above and other discoveries led to the recognition that reducing the levels of estrogen-DNA adducts would prevent the initiation of breast and other types of human cancer. We have found that the dietary supplements N-acetylcysteine and resveratrol inhibit estrogen-DNA adduct formation in both cultured human breast cells and in women. These results suggest that these two supplements offer an approach to reduce risk of developing breast and other types of human cancer.",
keywords = "Cancer prevention, Catechol estrogen-3,4-quinones, Estrogen genotoxicity, Estrogen mutagenicity, N-acetylcysteine, Resveratrol",
author = "Ercole Cavalieri and Rogan, {Eleanor G}",
year = "2016",
month = "1",
day = "1",
doi = "10.1007/978-3-319-27135-4_6",
language = "English (US)",
isbn = "9783319271330",
pages = "113--145",
booktitle = "Trends in Breast Cancer Prevention",
publisher = "Springer International Publishing",

}

TY - CHAP

T1 - Inhibition of depurinating estrogen-DNA adduct formation in the prevention of breast and other cancers

AU - Cavalieri, Ercole

AU - Rogan, Eleanor G

PY - 2016/1/1

Y1 - 2016/1/1

N2 - One problem in the efforts to prevent breast cancer has been the lack of recognition that estrogens can initiate cancer by acting as chemical carcinogens and reacting with DNA. Specific metabolites of endogenous estrogens, the catechol estrogen-3,4-quinones, react with DNA to form depurinating estrogen-DNA adducts. Loss of these adducts leaves apurinic sites in the DNA, generating mutations that can lead to the initiation of cancer. If estrogen metabolism becomes unbalanced and generates excessive catechol estrogen-3,4-quinones, formation of depurinating estrogen-DNA adducts and the risk of initiating cancer increase. Inhibiting formation of depurinating estrogen-DNA adducts can, therefore, prevent cancer. Levels of the estrogen-DNA adducts are high in women diagnosed with breast cancer and those at high risk for the disease. The finding that high levels of depurinating estrogen-DNA adducts precede the presence of breast cancer indicates that formation of these adducts is a critical factor in breast cancer initiation. Women with thyroid or ovarian cancer also have high levels of estrogen-DNA adducts, as do men with prostate cancer or non-Hodgkin lymphoma. The findings summarized above and other discoveries led to the recognition that reducing the levels of estrogen-DNA adducts would prevent the initiation of breast and other types of human cancer. We have found that the dietary supplements N-acetylcysteine and resveratrol inhibit estrogen-DNA adduct formation in both cultured human breast cells and in women. These results suggest that these two supplements offer an approach to reduce risk of developing breast and other types of human cancer.

AB - One problem in the efforts to prevent breast cancer has been the lack of recognition that estrogens can initiate cancer by acting as chemical carcinogens and reacting with DNA. Specific metabolites of endogenous estrogens, the catechol estrogen-3,4-quinones, react with DNA to form depurinating estrogen-DNA adducts. Loss of these adducts leaves apurinic sites in the DNA, generating mutations that can lead to the initiation of cancer. If estrogen metabolism becomes unbalanced and generates excessive catechol estrogen-3,4-quinones, formation of depurinating estrogen-DNA adducts and the risk of initiating cancer increase. Inhibiting formation of depurinating estrogen-DNA adducts can, therefore, prevent cancer. Levels of the estrogen-DNA adducts are high in women diagnosed with breast cancer and those at high risk for the disease. The finding that high levels of depurinating estrogen-DNA adducts precede the presence of breast cancer indicates that formation of these adducts is a critical factor in breast cancer initiation. Women with thyroid or ovarian cancer also have high levels of estrogen-DNA adducts, as do men with prostate cancer or non-Hodgkin lymphoma. The findings summarized above and other discoveries led to the recognition that reducing the levels of estrogen-DNA adducts would prevent the initiation of breast and other types of human cancer. We have found that the dietary supplements N-acetylcysteine and resveratrol inhibit estrogen-DNA adduct formation in both cultured human breast cells and in women. These results suggest that these two supplements offer an approach to reduce risk of developing breast and other types of human cancer.

KW - Cancer prevention

KW - Catechol estrogen-3,4-quinones

KW - Estrogen genotoxicity

KW - Estrogen mutagenicity

KW - N-acetylcysteine

KW - Resveratrol

UR - http://www.scopus.com/inward/record.url?scp=85008937620&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008937620&partnerID=8YFLogxK

U2 - 10.1007/978-3-319-27135-4_6

DO - 10.1007/978-3-319-27135-4_6

M3 - Chapter

AN - SCOPUS:85008937620

SN - 9783319271330

SP - 113

EP - 145

BT - Trends in Breast Cancer Prevention

PB - Springer International Publishing

ER -