25 Citations (Scopus)

Abstract

Bisphenol A (BPA) displays weak estrogenic properties and could be a weak carcinogen by a mechanism similar to that of estrone (E1), estradiol (E2) and the synthetic estrogen diethylstilbestrol, a human carcinogen. A wide variety of scientific evidence supports the hypothesis that certain estrogen metabolites, predominantly catechol estrogen-3,4-quinones, react with DNA to cause mutations that can lead to the initiation of cancer. One of the major pathways of estrogen metabolism leads to the 4-catechol estrogens, 4-OHE1(E2), which are oxidized to their quinones, E 1(E2)-3,4-Q. The quinones react with DNA to form predominantly the depurinating adducts 4-OHE1(E2)-1-N3Ade and 4-OHE1(E2)-1-N7Gua. This process constitutes the predominant pathway in the initiation of cancer by estrogens. One pathway of BPA metabolism is hydroxylation of one of its symmetric benzene rings to form its catechol, 3-OHBPA. Subsequent oxidation to BPA-3,4-quinone would lead to reaction with DNA to form predominantly the depurinating adducts 3-OHBPA-6-N3Ade and 3-OHBPA-6-N7Gua. The resulting apurinic sites in the DNA could generate mutations in critical genes that can initiate human cancers. The catechol of BPA may also alter expression of estrogen-activating and deactivating enzymes, and/or compete with methoxylation of 4-OHE1(E2) by catechol-O-methyltransferase, thereby unbalancing the metabolism of estrogens to increase formation of E1(E2)-3,4-Q and the depurinating estrogen-DNA adducts leading to cancer initiation. Thus, exposure to BPA could increase the risk of developing cancer by direct and/or indirect mechanisms. Knowledge of these mechanisms would allow us to begin to understand how BPA may act as a weak carcinogen and would be useful for regulating its use.

Original languageEnglish (US)
Pages (from-to)746-751
Number of pages6
JournalIUBMB Life
Volume62
Issue number10
DOIs
StatePublished - Oct 1 2010

Fingerprint

Diethylstilbestrol
Carcinogens
Estrogens
Metabolism
Quinones
DNA
Neoplasms
Catechol Estrogens
Estradiol Congeners
Catechol O-Methyltransferase
Hydroxylation
Mutation
DNA Adducts
Estrone
Metabolites
Benzene
bisphenol A
Estradiol
Genes
Oxidation

Keywords

  • bisphenol A as carcinogen
  • catechol estrogen
  • catechol quinones
  • estrogens
  • molecular mechanism of cancer initiation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Clinical Biochemistry
  • Cell Biology

Cite this

Is bisphenol A a weak carcinogen like the natural estrogens and diethylstilbestrol? / Cavalieri, Ercole; Rogan, Eleanor G.

In: IUBMB Life, Vol. 62, No. 10, 01.10.2010, p. 746-751.

Research output: Contribution to journalArticle

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abstract = "Bisphenol A (BPA) displays weak estrogenic properties and could be a weak carcinogen by a mechanism similar to that of estrone (E1), estradiol (E2) and the synthetic estrogen diethylstilbestrol, a human carcinogen. A wide variety of scientific evidence supports the hypothesis that certain estrogen metabolites, predominantly catechol estrogen-3,4-quinones, react with DNA to cause mutations that can lead to the initiation of cancer. One of the major pathways of estrogen metabolism leads to the 4-catechol estrogens, 4-OHE1(E2), which are oxidized to their quinones, E 1(E2)-3,4-Q. The quinones react with DNA to form predominantly the depurinating adducts 4-OHE1(E2)-1-N3Ade and 4-OHE1(E2)-1-N7Gua. This process constitutes the predominant pathway in the initiation of cancer by estrogens. One pathway of BPA metabolism is hydroxylation of one of its symmetric benzene rings to form its catechol, 3-OHBPA. Subsequent oxidation to BPA-3,4-quinone would lead to reaction with DNA to form predominantly the depurinating adducts 3-OHBPA-6-N3Ade and 3-OHBPA-6-N7Gua. The resulting apurinic sites in the DNA could generate mutations in critical genes that can initiate human cancers. The catechol of BPA may also alter expression of estrogen-activating and deactivating enzymes, and/or compete with methoxylation of 4-OHE1(E2) by catechol-O-methyltransferase, thereby unbalancing the metabolism of estrogens to increase formation of E1(E2)-3,4-Q and the depurinating estrogen-DNA adducts leading to cancer initiation. Thus, exposure to BPA could increase the risk of developing cancer by direct and/or indirect mechanisms. Knowledge of these mechanisms would allow us to begin to understand how BPA may act as a weak carcinogen and would be useful for regulating its use.",
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AU - Rogan, Eleanor G

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N2 - Bisphenol A (BPA) displays weak estrogenic properties and could be a weak carcinogen by a mechanism similar to that of estrone (E1), estradiol (E2) and the synthetic estrogen diethylstilbestrol, a human carcinogen. A wide variety of scientific evidence supports the hypothesis that certain estrogen metabolites, predominantly catechol estrogen-3,4-quinones, react with DNA to cause mutations that can lead to the initiation of cancer. One of the major pathways of estrogen metabolism leads to the 4-catechol estrogens, 4-OHE1(E2), which are oxidized to their quinones, E 1(E2)-3,4-Q. The quinones react with DNA to form predominantly the depurinating adducts 4-OHE1(E2)-1-N3Ade and 4-OHE1(E2)-1-N7Gua. This process constitutes the predominant pathway in the initiation of cancer by estrogens. One pathway of BPA metabolism is hydroxylation of one of its symmetric benzene rings to form its catechol, 3-OHBPA. Subsequent oxidation to BPA-3,4-quinone would lead to reaction with DNA to form predominantly the depurinating adducts 3-OHBPA-6-N3Ade and 3-OHBPA-6-N7Gua. The resulting apurinic sites in the DNA could generate mutations in critical genes that can initiate human cancers. The catechol of BPA may also alter expression of estrogen-activating and deactivating enzymes, and/or compete with methoxylation of 4-OHE1(E2) by catechol-O-methyltransferase, thereby unbalancing the metabolism of estrogens to increase formation of E1(E2)-3,4-Q and the depurinating estrogen-DNA adducts leading to cancer initiation. Thus, exposure to BPA could increase the risk of developing cancer by direct and/or indirect mechanisms. Knowledge of these mechanisms would allow us to begin to understand how BPA may act as a weak carcinogen and would be useful for regulating its use.

AB - Bisphenol A (BPA) displays weak estrogenic properties and could be a weak carcinogen by a mechanism similar to that of estrone (E1), estradiol (E2) and the synthetic estrogen diethylstilbestrol, a human carcinogen. A wide variety of scientific evidence supports the hypothesis that certain estrogen metabolites, predominantly catechol estrogen-3,4-quinones, react with DNA to cause mutations that can lead to the initiation of cancer. One of the major pathways of estrogen metabolism leads to the 4-catechol estrogens, 4-OHE1(E2), which are oxidized to their quinones, E 1(E2)-3,4-Q. The quinones react with DNA to form predominantly the depurinating adducts 4-OHE1(E2)-1-N3Ade and 4-OHE1(E2)-1-N7Gua. This process constitutes the predominant pathway in the initiation of cancer by estrogens. One pathway of BPA metabolism is hydroxylation of one of its symmetric benzene rings to form its catechol, 3-OHBPA. Subsequent oxidation to BPA-3,4-quinone would lead to reaction with DNA to form predominantly the depurinating adducts 3-OHBPA-6-N3Ade and 3-OHBPA-6-N7Gua. The resulting apurinic sites in the DNA could generate mutations in critical genes that can initiate human cancers. The catechol of BPA may also alter expression of estrogen-activating and deactivating enzymes, and/or compete with methoxylation of 4-OHE1(E2) by catechol-O-methyltransferase, thereby unbalancing the metabolism of estrogens to increase formation of E1(E2)-3,4-Q and the depurinating estrogen-DNA adducts leading to cancer initiation. Thus, exposure to BPA could increase the risk of developing cancer by direct and/or indirect mechanisms. Knowledge of these mechanisms would allow us to begin to understand how BPA may act as a weak carcinogen and would be useful for regulating its use.

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