title: Influence of asbestos on the uptake of benzo(a)pyrene and DNA alkylation in hamster tracheal epithelial cells.
abstract: The objective of these experiments was to understand the mechanism of cocarcinogenicity of asbestos and polycyclic aromatic hydrocarbons. Benzo(a)pyrene [B(a)P] was coated onto crocidolite or chrysotile asbestos fibers, resuspended in serum-free medium, and added to cultures of hamster tracheal epithelial cells. The fibers markedly enhanced cell uptake of B(a)P. Although considerable metabolism occurred, approximately 40% of the applied B(a)P was retained by the cells after 8-hr incubation as opposed to 5% after incubation with B(a)P in the absence of asbestos. The hydrocarbon-containing medium was replaced by fresh medium. Four days later, approximately 3% of the B(a)P that had been applied when adsorbed to asbestos was still persistent in cells as compared to 0.5% in cells treated with B(a)P alone. DNA from hamster tracheal epithelial cells was purified, and the amount of B(a)P alkylation was assessed. At 8 hr, the extent of alkylation after treatment of the cells with either B(a)P or B(a)P:asbestos was similar. However, the retained unmetabolized B(a)P was subsequently metabolized and contributed to further alkylation so that the B(a)P-asbestos treated cells demonstrated considerably higher levels of alkylation throughout the 4-day posttreatment period. None of these effects was observed if asbestos was added 1 hr before the addition of B(a)P. The enhanced uptake of B(a)P and subsequent additional alkylation of DNA might represent a mechanism of asbestos-induced cocarcinogenesis.
mesh_terms: D000478:Alkylation; D000818:Animals; D001194:Asbestos / Q000494:pharmacology*; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D004357:Drug Synergism; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001580:Benzopyrenes; D001194:Asbestos; D001564:Benzo(a)pyrene; D004247:DNA