We propose to conduct two related molecular epidemiological studies to characterize and validate five different markers of biologically effective dose in worker populations with well-characterized and substantial exposure to the mutagenic and carcinogenic chemicals: ethylene oxide (EtO) and styrene. The markers will include DNA- (lymphocyte) and protein- (hemoglobin) adducts, sister chromatid exchange, micronuclei in lymphocytes and unscheduled DNA synthesis. This battery of genetic markers will all be performed on the same blood sample to provide comparable data. This study will provide information on three different mechanisms involved in carcinogenesis: covalent binding to DNA, chromosomal damage, and DNA repair. The markers used will also provide comparative information on long-term exposure (refected by lymphocyte DNA0 and that incurred during the last four months (hemoglobin). Extensive workplace and personal monitoring will be carried out to fully characterize current ambient exposures; these data will be related to assay measurements. Data on historical exposures to these chemicals, on other relevant exposures and on potential confounding variables will be gathered by questionnaire. Although prior human studies have demonstrated that EtO and styrene can induce the biological effects to be measured here, most have been limited with respect to exposrue data and control of potential confounding variables. Moreover, none has applied a combination or """"""""battery"""""""" of methods. This approach has the advantage of being cost-effective since major costs are incurred during the collection and initial processing of samples and in obtaining exposure and questionnaire data. Running multiple assays on the same samples allows significant cost-saving and permits evaluation of the relative cost-effectiveness of each method.
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