Influence of asbestos on the uptake of benzo(a)pyrene and DNA alkylation in hamster tracheal epithelial cells.
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.
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*
D001580:Benzopyrenes; D001194:Asbestos; D001564:Benzo(a)pyrene; D004247:DNA