These studies will focus on the development and use of techniques to monitor human exposure to crude coal tar (CCT). Dermatologic patients will be used as a model population for occupational exposures involving dermal absorption. A panel of biological markers will be measured in 40-50 CCT treated psoriasis patients and an equal number of controls. Previously developed antibodies recognizing benzo (a) pyrene (BP) and other polycyclic aromatic hydrocarbon (PAH) diol expoxide-DNA adducts will be used to monitor adduct formation in lymphocytes by competitive enzyme linked immunosorbent assay (ELISA). These same antibodies will be used in indirect immunofluorescence studies to localize adduct formation in skin biopsies from treated patients. Total PAH-DNA adducts in lymphocytes will also be monitored using the 32P postlabeling technique. BP adducts on hemoglobin will be monitored in an ELISA using antibodies which recognize the modified protein. Monoclonal antibodies will be developed which recognize BP itself as well as it metabolites. These antibodies will be characterized as to sensitivity and specificity by ELISA and then used to monitor levels of BP and its metabolites in sera and urine. Sera will be monitored for the presence of antibodies which recognize BP-protein or DNA adducts as an alternate indicator of adduct formation in vivo. Mutagens in urine will be monitored with the Salmonella typhimurium mutagenesis assay. Levels of the different biological markers will be correlated with exposure. These studies will thus develop and validate methods to monitor the biological effects of human exposure to PAHs and serve as a model system for skin exposure.
| Santella, R M; Zhang, Y J; Young, T L et al. (1991) Monitoring human exposure to environmental carcinogens. Adv Exp Med Biol 283:165-81 |
| Gomes, M; Santella, R M (1990) Immunologic methods for the detection of benzo[a]pyrene metabolites in urine. Chem Res Toxicol 3:307-10 |
| Zhang, Y J; Li, Y; DeLeo, V A et al. (1990) Detection of DNA adducts in skin biopsies of coal tar-treated psoriasis patients: immunofluorescence and 32P postlabeling. Skin Pharmacol 3:171-9 |
| Hatch, M C; Warburton, D; Santella, R M (1990) Polycyclic aromatic hydrocarbon-DNA adducts in spontaneously aborted fetal tissue. Carcinogenesis 11:1673-5 |
