Spectral Characterization of Catechol Estrogen Quinone (CEQ)-Derived DNA Adducts and Their Identification in Human Breast Tissue Extract

Markushin, Yuri; Zhong, Wenwan; Cavalieri, Ercole L.; Rogan, Eleanor G.; Small, Gerald J.; Yeung, E.S.; Jankowiak, Ryszard

doi:10.1021/tx0340854

Cited by 59 publications

(68 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although evidence from cell-culture and animal studies support the estrogen adduct-mediated pathway for the referred cancers, data from humans are scarce. Some authors have reported the presence of 4-OH-E1-1-N3Ade at 8.4 pmol/g in breast tissue from a woman with carcinoma (17), and a non-depurinating hydroxyestradiol guanosine found upon hydrolysis of DNA from breast tissues (18). Interestingly, urine levels of 4-OH-E1-1-N3Ade are low in men with prostate cancer or other urological problems (17), whereas a study involving 76 women showed high urine levels of this estrogen adduct in women at high risk of or with breast cancer, as compared to controls (19).…”

Section: Discussionmentioning

confidence: 99%

“…Some authors have reported the presence of 4-OH-E1-1-N3Ade at 8.4 pmol/g in breast tissue from a woman with carcinoma (17), and a non-depurinating hydroxyestradiol guanosine found upon hydrolysis of DNA from breast tissues (18). Interestingly, urine levels of 4-OH-E1-1-N3Ade are low in men with prostate cancer or other urological problems (17), whereas a study involving 76 women showed high urine levels of this estrogen adduct in women at high risk of or with breast cancer, as compared to controls (19). Convert et al (20) developed an LC-MS/MS method for assessment of the reactivity of estradiol-2,3-quinone towards deoxyribonucleosides in crude reaction mixtures and proved that LC-ESI-MSn is a very powerful analytical tool for the detection of DNA-estrogen adducts generated in vivo.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inactivation of estrogen receptor by Schistosoma haematobium total antigen in bladder urothelial cells

Botelho¹

2011

Oncol Rep

View full text Add to dashboard Cite

Abstract.We recently reported the expression of an estradiollike molecule by a trematode parasite Schistosoma haematobium. We further established that this estradiol-like molecule is an antagonist of estradiol, repressing the transcriptional activity of the estrogen receptor (ER) in estrogen-responsive MCF7 cells and also that S. haematobium total antigen (Sh) contains estrogenic molecules detected by mass spectrometry. In the present study, we used HCV29 cells, a cell line derived from normal urothelial cells, as well as an in vivo model to evaluate the expression of ER in the bladders of Sh-instilled animals. We show that, similarly to MCF7 cells, Sh down-regulates the transcriptional activity of ER in HCV29 cells and also in the bladders of Sh-treated mice. The antiestrogenic activity of the S. haematobium extract and its repressive role in ER could have implications in the carcinogenic process in bladders with S. haematobium infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inactivation of estrogen receptor by Schistosoma haematobium total antigen in bladder urothelial cells

Botelho¹

2011

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…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%

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

Zahid

Saeed

et al. 2007

Free Radical Biology and Medicine

View full text Add to dashboard Cite

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.

show abstract

“…3,4 The discovery that specific oxidative metabolites of estrogens, namely, catechol estrogen quinones, can react with DNA [5][6][7][8][9] led to and supports the hypothesis that these metabolites can become endogenous chemical carcinogens. Some of the mutations generated by this specific DNA damage can result in the initiation of cancer.…”

mentioning

confidence: 96%

The molecular etiology of breast cancer: Evidence from biomarkers of risk

Gaikwad

Yang

Muti³

et al. 2008

Intl Journal of Cancer

117

221

View full text Add to dashboard Cite

Estrogens can become endogenous carcinogens via formation of catechol estrogen quinones, which react with DNA to form specific depurinating estrogen-DNA adducts. The mutations resulting from these adducts can lead to cell transformation and the initiation of breast cancer. Estrogen metabolites, conjugates and depurinating DNA adducts in urine samples from 46 healthy control women, 12 high-risk women and 17 women with breast cancer were analyzed. The estrogen metabolites, conjugates and depurinating DNA adducts were identified and quantified by using ultraperformance liquid chromatography/tandem mass spectrometry. The levels of the ratios of depurinating DNA adducts to their respective estrogen metabolites and conjugates were significantly higher in high-risk women (p < 0.001) and women with breast cancer (p < 0.001) than in control subjects. The high-risk and breast cancer groups were not significantly different (p 5 0.62). After adjusting for patient characteristics, these ratios were still significantly associated with health status. Thus, the depurinating estrogen-DNA adducts are possible biomarkers for early detection of breast cancer risk and response to preventive treatment. ' 2007 Wiley-Liss, Inc.Key words: breast cancer risk; depurinating estrogen-DNA adducts; estrogen biomarkers; balance in estrogen metabolism Development of noninvasive tests of breast cancer risk has been a major goal for more than 30 years. In this article we present biomarkers of risk that are related to the hypothesized first critical step in the initiation of breast cancer, namely, the reaction of catechol estrogen quinone metabolites with DNA.1 Prevention of cancer can be achieved by blocking this DNA damage, which generates the mutations leading to the initiation, promotion and progression of cancer. 2Exposure to estrogens is a known risk factor for breast cancer.3,4 The discovery that specific oxidative metabolites of estrogens, namely, catechol estrogen quinones, can react with DNA [5][6][7][8][9] led to and supports the hypothesis that these metabolites can become endogenous chemical carcinogens. Some of the mutations generated by this specific DNA damage can result in the initiation of cancer. 1,5 This paradigm suggests that specific, critical mutations generate abnormal cell proliferation leading to cancer. 1,[10][11][12][13] As illustrated in Figure 1, in the metabolism of catechol estrogens there are activating pathways 14 that lead to the formation of the estrogen quinones, estrone (estradiol) quinones [E 1 (E 2 )-Q], which can react with DNA. There are also deactivating pathways that limit formation of the quinones and/or prevent their reaction with DNA. These are methylation of catechol estrogens, 15 conjugation of the E 1 (E 2 )-Q with glutathione (GSH) 16 and reduction of the quinones to catechols 17 (Fig. 1). When E 1 (E 2 )-3,4-Q react with DNA, they form predominantly the depurinating adducts 4-hydroxyestrone(estradiol)-1-N3Ade-nine [4-OHE 1 (E 2 )-1-N3Ade] and 4-hydroxyestrone(estradiol)-1-N7Guanine [4-OHE 1 (E 2...

show abstract

Spectral Characterization of Catechol Estrogen Quinone (CEQ)-Derived DNA Adducts and Their Identification in Human Breast Tissue Extract

Cited by 59 publications

References 52 publications

Inactivation of estrogen receptor by Schistosoma haematobium total antigen in bladder urothelial cells

Inactivation of estrogen receptor by Schistosoma haematobium total antigen in bladder urothelial cells

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

The molecular etiology of breast cancer: Evidence from biomarkers of risk

Contact Info

Product

Resources

About