Benzo(a)pyrene (BaP) is a well known and ubiquitous environmental carcinogen. Epidemiologic and animal data have shown that coadministered industrial particles, e.g., ferric oxide, can facilitate the tumorigenicity of BaP. From an occupational perspective, exposure to particulates almost always includes polycyclic aromatic hydrocarbons (PAH). In regard to the biological responses of the host, alveolar macrophages (AM) possess two essential functions: phagocytosis and metabolism. However, the target tissues in 90% of human lung cancers are bronchogenic epithelial cells. Based upon the host defense response and the target tissue, cocultivation system has been established which involved AM and tracheal epithelial cell. Our interest is to investigate the alteration of BaP metabolism, the binding of DNA and the types of DNA-adduct in BaP-coated ferric oxide and aluminum oxide in this coculture system. The profile of BaP metabolites, the amount and the type of DNA-adducts formation in this coculture system may provide us with some insights upon the role of the particles in the mechanism of carcinogenicity.
The specific aims are: l. To determine the alteration of basal metabolic activities of AM in response to BaP and BaP- coated particles. 2. To determine the pattern and the amount of BaP metabolites, in particular, 7, 8-diol-BaP, the precursor of the ultimate carcinogen, following incubation of radiolabeled BaP or BaP-coated particles with AM. 3. To determine the profile and extent of DNA-adducts in the target epithelial cells, in particular, the 7, 8-diol-9, 10-BaP-dGuo (BPDEI-dGuo) (trans/cis), in the cocultivation system in which AM are treated with BaP alone or BaP-coated particles.
| Warshawsky, D; Reilman, R; Cheu, J et al. (1994) Influence of particle dose on the cytotoxicity of hamster and rat pulmonary alveolar macrophage in vitro. J Toxicol Environ Health 42:407-21 |
