Abstract 603: Signatures of chemoprotection from ambient exposure to outdoor air pollution in the human serum albumin Cys34 adductome
Authors: Joshua W. Smith, Robert N. O'Meally, Derek Ng, Thomas W. Kensler, Robert N. Cole, John D. Groopman
Journal: Cancer Research (2019)

Abstract Many components of outdoor air pollution, such as benzene, are known to be carcinogenic to humans. However, due to spatial and temporal variation in air pollution, ambient measures of single pollutant exposures may be limited for generalizing across diverse settings. Covalent adducts of air pollutants with the free thiol at the Cys34 residue of human serum albumin represent biomarkers of recent air pollution exposure (&amp;lt;3 months), while adductomic interrogation enables characterization of exposures to complex air pollution mixtures. We have used Cys34 adductomics to further characterize the protective effects of a successful intervention trial in the Yangtze River delta - a region characterized by consistent and substantial levels of airborne pollution, as well as a rising incidence of lung cancer. Residents of Qidong, China were recruited to participate in a 12-week, randomized, placebo-controlled clinical trial. Participants consumed either a placebo (P) or broccoli sprout beverage (B) daily, and urine and serum samples were collected before and throughout the intervention. Previously published results revealed that, relative to P treatment, B significantly increased detoxication and urinary excretion of benzene (+61%, as S-phenylmercapturic acid [SPMA]). For this pilot study, the serum albumin Cys34adductome was interrogated in n=8 non-smoking women at study day 56 from each of the P and B treatment groups, selecting subjects whose day 56 SPMA excretion was closest to their respective group’s geometric mean. Albumin was precipitated from serum, digested with lysyl endopeptidase, separated by nanoflow LC, and Cys34adducts were identified and quantified on a Thermo Scientific Orbitrap Fusion Tribrid mass spectrometer. We detected four serum albumin Cys34 adducts arising from three metabolites of benzene: benzoquinone (BQ; BQ1 and BQ2), benzene oxide (BO), and benzene diolepoxide (BDE). In accordance with elevated urinary SPMA excretion, BO levels trended lower with B treatment (-39%, p=0.06), while BQ2 was strongly and significantly diminished (-51%, p=0.005); no effect was observed in BQ1 or BDE adduct levels. Incubation of 1,4-BQ with human serum in vitro suggested that the BQ adducts observed in vivo reflect keto-enol tautomerism of a 1,4-BQ-derived adduct, rather than 1,4-BQ and its structural isomer, 1,2-BQ. Along with benzene-derived adducts, we identified several other putative adducts (cyano, ethylene oxide, aldehydes, oxidation, mixed disulfides), revealing a multidimensional signature. To our knowledge, this is the first report to detect benzene-derived adducts, using an adductomics approach, in humans with only ambient exposures. Work is underway to expand upon these results. Cys34 adductomics represents a promising approach for the discovery and quantification of air pollution exposure biomarkers. Citation Format: Joshua W. Smith, Robert N. O'Meally, Derek Ng, Thomas W. Kensler, Robert N. Cole, John D. Groopman. Signatures of chemoprotection from ambient exposure to outdoor air pollution in the human serum albumin Cys34 adductome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 603.