Abstract 4641: Cumulative body burdens of polycyclic aromatic hydrocarbons associate with estrogen bioactivation in pregnant women: Protein adducts as biomarker of exposure
Authors: Po-Hsiung Lin, Tzu-Wen Wang, Chen-His Tsai, Hz-Han Wei, Guan-Jie Chen, Dar-Ren Chen, Shou-Tung Chen, Shu-Li Wang, Che Lin
Journal: Cancer Research (2011)

Abstract The objective of this research was to develop a biochemical assay to simultaneously analyze protein adducts of quinonoid metabolites of polycyclic aromatic hydrocarbons (PAHs) and endogenous estrogen in pregnant women in Taiwan and to explore the correlations among them. The methodology, which employs trifluoroacetic acid anhydride (TFAA) and methanesulfonic acid (MSA) to selectively cleave cysteinyl adducts, had previously been applied to measure benzene and naphthalene adducts in albumin (Alb). In this study, we refined the assay to allow measurements of both naphthoquinone- and estrogen quinone-derived adducts in serum albumin derived from pregnant women in Taiwan. The isomeric forms of cysteinyl adducts of naphthoquinones, including 1,2-naphthoquinone (1,2-NPQ) and 1,4-naphthoquinone (1,4-NPQ) as well as estrogen quinones, including estrogen-2,3-quinones (E2-2,3-Q) and estrogen-3,4-quinones (E2-3,4-Q), are characterized by using isotopically-labelled bound internal standards after adducts cleavage by the TFAA/MSA derivatization procedure. We applied this method to analyze the background levels of cysteinyl adducts of naphthalene- and estrogen-derived quinones on human serum albumin(Alb)derived from healthy pregnant women (n=40) and their respective umbilical cords (n=40). Results showed that the background levels of cysteinyl adducts of 1,2-NPQ and 1,4-NPQ on human serum albumin were at levels ranging from 89-941 and 33-615 pmol/g, respectively. Logged levels of 1,2-NPQ-Alb were correlated with logged levels of 1,4-NPQ-Alb (correlation coefficient r=0.500, p&amp;lt;0.001). In addition, cysteinyl adducts of E2-2,3-Q-1-S-Alb, E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb were detected in most of the subjects with median levels at 325, 457, and 592 pmol/g, respectively. We also found a significantly positive relationship between logged levels of E2-2,3-Q-4-S-Alb and those of E2-3,4-Q-2-S-Alb (r = 0.537, p&amp;lt;0.001). We noticed that logged levels of 1,2-NPQ-Alb are positively and significantly associated with increasing logged levels of E2-3,4-Q-2-S-Alb (r = 0.539, p&amp;lt;0.001). This evidence suggests that environmental exposure to PAHs may enhance the production of reactive quinone species of endogenous estrogen in human. Overall, we conclude that the methodology developed in this study may be applied to epidemiological study to serve as biomarkers of environmental exposure to PAHs and other modulators of estrogen homeostasis. (This work was supported by the National Science Council, Taiwan, through grant NSC99-2314-B-005-001-MY3) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4641. doi:10.1158/1538-7445.AM2011-4641