Abstract 4712: Characterization of estrogen quinone-derived protein adducts and their identification in human serum albumin
| Autor: | Tzu-Wen Wang, Tzu-Han Wei, Po-Hsiung Lin, Tsung-Chou Yang, Dar-Ren Chen |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | Cancer Research. 70:4712-4712 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Both estrogen-2,3-quinone (E2-2,3-Q) and estrogen-3,4-quinone (E2-3,4-Q) are reactive metabolites of estrogen that are thought to be responsible for the estrogen-induced genotoxicity. The aim of this study was to establish a methodology to analyze estrogen quinone-derived protein adducts and to measure the background levels of these adducts in human serum albumin (Alb) derived from female blood donors in Taiwan. The methodology, which employs trifluoroacetic acid anhydride and methanesulfonic acid to selectively cleave cysteinyl adducts, had previously been applied to measure naphthalene adducts in blood proteins. Results from in vitro experiments confirmed that the production of estrogen quinone-derived adducts on serum albumin increased with increased concentration of estrogen quinones (0-100 nM). The average formation of estrogen quinone-derived cysteinyl adducts per unit concentration of estrogen quinones was estimated to be 13.0, 48.2, and 36.1 (pmol/g Alb)/(nM) for E2-2,3-Q-1-S-Alb, E2-2,3-Q-4-S-Alb, and E2-3,4-Q-2-S-Alb, respectively. Time-course experiments indicated that both E2-2,3-Q- and E2-3,4-Q-derived adducts rapidly reached maximum values at 10 min mark and remained constant thereafter. Additionally, with 2,3,7,8-tetrachlorodibenzo-p-dioxin pretreatment (10 nM for 72 h), production of estrogen quinone-derived protein adducts was also detected in human MCF-7 breast cancer cells exposed to estrogen (1 μM for 9 h). Co-treatment of Ro 41-0960, a catechol-o-methyl transferase inhibitor, further enhanced the production of estrogen quinone-derived adducts in all cases. When we investigated the levels of estrogen quinone-derived adducts in human serum Alb derived from female blood donors in Taiwan, cysteinyl adducts of E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb were detected in all subjects (n=10). The median levels of E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb in human subjects were estimated to be 398 (range 240-807) and 39.0 (range 0.3-101) (pmol/g), respectively. We noticed that levels of E2-2,3-Q-4-S-Alb were significantly correlated with those of E2-3,4-Q-2-S-Alb (correlation coefficient r = 0.684, p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4712. |
| Databáze: | OpenAIRE |
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