Induction of A·T to G·C mutations by erroneous repair of depurinated DNA following estrogen treatment of the mammary gland of ACI rats

Mailander, Paula C.; Meza, Jane L.; Higginbotham, Sheila; Chakravarti, Dhrubajyoti

doi:10.1016/j.jsbmb.2006.06.019

Cited by 80 publications

(126 citation statements)

References 68 publications

(94 reference statements)

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“…Release of the depurinating adducts leaves apurinic sites in the DNA, which, in turn, induce mutations. It is thought that critical mutations generated by specific DNA damage can result in abnormal cell proliferation leading to cancer (Chakravarti et al 2001, Fernandez et al 2006, Mailander et al 2006, Zhao et al 2006, 2009a. All of these results support the hypothesis that estrogens could initiate NHL through the formation of depurinating DNA adducts.…”

Section: Introductionmentioning

confidence: 71%

Urinary biomarkers suggest that estrogen-DNA adducts may play a role in the aetiology of non-Hodgkin lymphoma

Gaikwad¹,

Yang²,

Weisenburger³

et al. 2009

Biomarkers

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A variety of evidence suggests that estrogens may induce non-Hodgkin lymphoma (NHL). The reaction of catechol estrogen quinones with DNA to form depurinating estrogen-DNA adducts is hypothesized to initiate this process. These adducts are released from DNA, shed from cells into the bloodstream and excreted in urine. The aim of this study was to determine whether or not the depurinating estrogen-DNA adducts might be involved in the aetiology of human NHL. Estrogen metabolites, conjugates and depurinating DNA adducts were identified and quantified in spot urine samples from 15 men with NHL and 30 healthy control men by using ultraperformance liquid chromatography/tandem mass spectrometry. The levels of estrogen-DNA adducts were significantly higher in the men with NHL than in the healthy control men. Thus, formation of estrogen-DNA adducts may play a critical role in the aetiology of NHL, and these adducts could be potential biomarkers of NHL risk.

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Section: Introductionmentioning

confidence: 71%

Urinary biomarkers suggest that estrogen-DNA adducts may play a role in the aetiology of non-Hodgkin lymphoma

Gaikwad¹,

Yang²,

Weisenburger³

et al. 2009

Biomarkers

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“…Experiments on estrogen metabolism [6][7][8][9][10], formation of DNA adducts [11][12][13][14][15][16][17], mutagenicity [17][18][19][20][21], cell transformation [22][23][24] and carcinogenicity [25][26][27][28] have led to the hypothesis that certain estrogen metabolites, predominantly catechol estrogen-3,4-quinones, react with DNA to cause the mutations leading to the initiation of cancer ( Fig. 1) [17].…”

Section: Introductionmentioning

confidence: 99%

“…These adducts are lost from DNA by destabilization of the glycosyl bond. The apurinic sites generated in the DNA can produce mutations by error-prone repair [18][19][20], which in turn can lead to initiation of cancer.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of catechol-O-methyltransferase increases estrogen–DNA adduct formation

Zahid

Saeed

et al. 2007

Free Radical Biology and Medicine

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The association found between breast cancer development and prolonged exposure to estrogens suggests that this hormone is of etiologic importance in the causation of the disease. Studies on estrogen metabolism, formation of DNA adducts, carcinogenicity, cell transformation and mutagenicity have led to the hypothesis that reaction of certain estrogen metabolites, predominantly catechol estrogen-3,4-quinones, with DNA forms depurinating adducts [4-OHE 1 (E 2 )-1-N3Ade and 4-OHE 1 (E 2 )-1-N7Gua]. These adducts cause mutations leading to the initiation of breast cancer. Catechol-O-methyltransferase (COMT) is considered an important enzyme that protects cells from the genotoxicity and cytotoxicity of catechol estrogens, by preventing their conversion to quinones. The goal of the present study was to investigate the effect of COMT inhibition on the formation of depurinating estrogen-DNA adducts. Immortalized human breast epithelial MCF-10F cells were treated with 4-OHE 2 (0.2 or 0.5 μM) for 24 h at 120, 168, 216, and 264 h post-plating or one time at 1-30 μM 4-OHE 2 with or without the presence of COMT inhibitor (Ro41-0960). The culture media were collected at each point, extracted by solid-phase extraction and analyzed by HPLC connected with a multichannel electrochemical detector. The results demonstrate that MCF-10F cells oxidize 4-OHE 2 to E 1 (E 2 )-3,4-Q, which react with DNA to form the depurinating N3Ade and N7Gua adducts. The COMT inhibitor Ro41-0960 blocked the methoxylation of catechol estrogens, with concomitant 3-4 fold increases in the levels of the depurinating adducts. Thus, low activity of COMT leads to higher levels of depurinating estrogen-DNA adducts that can induce mutations and initiate cancer.

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“…Carcinogens that form abasic sites have been shown to induce errors in BER, forming mutations that lead to cancer (2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

“…In breast cancer, the mutations can be induced by errors in the repair of the abasic sites generated by natural estrogens (4)(5)(6). In this mechanism, estrogen metabolism in the breast is altered, leading to an abnormal increase in the levels of catechol quinones, especially the estrogen-3,4-quinones, which react with DNA and almost exclusively form depurinating adducts (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Prevalence of BER gene polymorphisms in sporadic breast cancer

Ali

Meza

Rogan³

et al. 2008

Oncol Rep

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Abstract. Studies suggest that breast cancer is initiated by the induction of somatic mutations from errors in the base excision repair (BER) of endogenous estrogen-induced abasic sites. If so, the inheritance of certain polymorphic mutations in BER genes involved in the incorporation and management of such errors should increase the risk of breast cancer. To test this hypothesis, we examined breast tissues from 48 women (controls, histopathologically normal tissue from reduction mammoplasty) and 40 women with breast cancer (breast tumor-adjacent, histopathologically normal tissues) for the presence of reported polymorphic mutations in four BER genes. The breast tissues were obtained from the Cooperative Human Tissue Network-western division and from the University of Nebraska Medical Center. Using PCR-RFLP procedures, the XRCC1 gene was examined for Arg194Trp and Arg399Gln, APE1 for Asp148Glu, LIG3α for Arg780His and PARP1 for Pro377Ser mutations. The women in this study carried only the XRCC1 Arg399Gln polymorphism. This result was surprising because APE1 148Glu was reported to be frequently inherited (allele frequency, 0.47-0.495) by USA and European women. Thus, the USA women in our study are genetically different from those in the previous studies. Among the control women, 21 (43.75%) were Arg/ Arg wild-types, 20 (41.67%) were Arg/Gln heterozygotes and 7 (14.6%) were Gln/Gln homozygotes. Among the breast cancer cases, 11 (27.5%) were Arg/Arg wild-types, 16 (40%) were Arg/Gln heterozygotes and 13 (32.5%) were Gln/Gln homozygotes. Thus, the Gln allele was significantly more frequent in breast cancer cases (allele frequency, 0.52) than in controls (allele frequency, 0.35), suggesting that XRCC1 399Gln may enhance the risk of breast cancer. IntroductionBase excision repair (BER) has long been thought of as the guardian of the genome, responsible only for minimizing somatic mutations by correctly repairing endogenous base loss in DNA (1). Carcinogens that form abasic sites have been shown to induce errors in BER, forming mutations that lead to cancer (2-5).In breast cancer, the mutations can be induced by errors in the repair of the abasic sites generated by natural estrogens (4-6). In this mechanism, estrogen metabolism in the breast is altered, leading to an abnormal increase in the levels of catechol quinones, especially the estrogen-3,4-quinones, which react with DNA and almost exclusively form depurinating adducts (7-9). These adducts spontaneously dissociate from DNA to form abasic sites and generate mutations by BER errors (4,5).If erroneous BER is a mechanism of breast cancer, the polymorphic mutations in BER genes that increase mutagenesis would be expected to modify breast cancer risk. There is a limited amount of information about BER gene polymorphisms in breast cancer (10,11). Briefly, OGG1 Ser326Cys, APE1 Asp148Glu, PARP1 Val276Trp and LIG3α Arg780His did not show any significant association with breast cancer (12)(13)(14). On the other hand, in some studies, polymorphisms in the XRCC1 gene (Arg194...

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Induction of A·T to G·C mutations by erroneous repair of depurinated DNA following estrogen treatment of the mammary gland of ACI rats

Cited by 80 publications

References 68 publications

Urinary biomarkers suggest that estrogen-DNA adducts may play a role in the aetiology of non-Hodgkin lymphoma

Urinary biomarkers suggest that estrogen-DNA adducts may play a role in the aetiology of non-Hodgkin lymphoma

Inhibition of catechol-O-methyltransferase increases estrogen–DNA adduct formation

Prevalence of BER gene polymorphisms in sporadic breast cancer

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