Validation of Biomarkers in Humans Exposed to PAHs

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DESCRIPTION (provided by applicant): Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants due to significant contributions from incomplete combustion of fossil fuels and other organic materials. Exposure to PAHs has been associated with lung and skin cancer in occupational setting and a potential increased risk of cancer in humans exposed to PAHs at low ambient levels is now becoming a major public concern. In order to address this problem, a variety of biomarkers have been developed to index the exposure levels or biological effects of PAHs. However, the validity of their applications in risk assessment of PAHs at low levels is uncertain. This proposed study will mainly focus on validating these biomarkers in a Chinese population with broad ranges of exposures to PAHs. The biomarkers to be validated include urinary 1-hydroxypyrene, DNA and protein (hemoglobin and albumin) adducts as well as p53 protein. In addition, the polymorphisms of genes, including CYP1A1, microsomal epoxide hydrolase (mEH), GSTM1, and p53 genes, will be identified to assess gene-environment interactions. For this purpose, we will conduct a study with 5 projects included. The specific aims of this study are: (1) to determine if these candidate markers can at least reliably detect differences between workers with relatively high levels of exposure and unexposed subjects; (2) to examine the reproducibility of these biomarkers and to assess their inter-and intra-individual variabilities; (3) to estimate the effective half-lives of the exposure markers and to evaluate whether they relate to the most current exposure or to integrated exposures over a period of time; (4) to determine whether these markers can be reliably used to differentiate between unexposed subjects and exposed subjects at low ambient levels and to characterize their exposure-response relationships; (5) to investigate the specificity of these biomarkers and to identify possible effects of general confounding factors, such as smoking, diet, age, and gender on the levels of these markers; (6) To evaluate how gene polymorphisms of CYP1A1, GSTM1, mEH, and p53 interact with PAHs exposure in relation to the levels of all candidate biomarkers. The ultimate goal of this study is to determine whether or not these biomarkers can be useful as markers for risk assessment in humans exposed to PAHs at low ambient levels in future large scale epidemiological studies.