Superfund Research Program
Using Adductomic Signatures to Evaluate Risks of Superfund Chemicals
- Project Summary
Although reactive chemicals generated by exposures to benzene and arsenic, both prominent Superfund chemicals, are known to be responsible for human cancers, these molecules are generally overlooked in exposomic investigations because they are too reactive to be measured in blood. The researchers are investigating ‘signatures’ of exposure to benzene and arsenic by measuring adducts of human serum albumin (HSA) that are derived from reactive intermediates generated by these exposures. Using archived serum from their previous investigations of subjects with and without exposures to benzene and arsenic, the researchers are using an omics assay (‘adductomics’) to find signature HSA adducts over a wide range of exposures. In year two the researchers had measured 65 adducts in archived plasma from 211 workers with and without occupational exposure to benzene. In current year three they have processed these data with a bioinformatics/statistics package and selected five adducts that were associated with benzene exposure, two with higher levels and three with lower levels in exposed subjects. Also in year three, the researchers measured adducts in archived plasma from 103 subjects exposed to high and 97 subjects exposed to low levels of arsenic in drinking water. These arsenic samples will be processed in year four with bioinformatics/statistics to find adducts associated with arsenic exposure. As these lists of signature adducts are developed, the researchers will target them in archived serum from nonsmoking women in a large cohort study (Shanghai Women’s Health Study, SWHS) being conducted by the National Cancer Institute in Shanghai, China, to estimate lymphoid and myeloid cancer and lung-cancer risks arising from exposures to benzene and arsenic, respectively. These archived serum/plasma specimens, consisting of 376 lung cancer cases and matched controls (n = 752) and 114 cases of lymphoid and myeloid cancers and matched controls (n = 228) were recently received from the NCI repository and are scheduled for adductomics in year four.