We propose to conduct a series of related in vivo pilot studies that take the first steps toward validating a recently developed immunoassay for benzo[a]pyrene (BaP) covalently bound to DNA as a dosimeter for """"""""biologically effective dose"""""""" of the carcinogen. A secondary goal is to preliminarily evaluate the potential of the assay as an indicator of increased risk of lung cancer. Specifically we will investigate relatively unknown aspects of in vivo binding, including the sensitivity of the assay, """"""""dose-response"""""""" relationships, the persistence of the adduct, the extent of interindividual variation, the correlation between concentrations of adducts in lung and white blood cell DNA in laboratory animals, and the possibility that lung cancer patients have a greater tendency to bind BaP to DNA than controls. The research will consist of (1) experimental studies of limited numbers of laboratory animals and highly exposed cigarette smoking volunteers in which exposure to BaP will be controlled and (2) observational and clinical studies of coke oven workers and lung cancer cases and controls. DNA extracted from lung and blood samples of animals and blood samples of humans will be assayed by the same enzyme linked immunosorbent assay (ELISA). For the human subjects, results in the ELISA will be analysed in conjunction with data obtained by questionnaire concerning exposure to BaP and to a limited number of agents believed to modify BaP metabolism in humans. This work is intended to verify and extend results of an earlier pilot project involving laboratory animals and hospital patients in order to develop meaningful data on the potential usefulness of the BaP-DNA assay for use as a dosimeter in future molecular epidemiological studies in cancer causation, and as a means of screening individuals who might be at elevated risk of lung cancer.
Showing the most recent 10 out of 22 publications
