Binding of (3H)benzo(a)pyrene to DNA in cultured human bronchus.
The studies reported here demonstrate some of the factors affecting the binding of benzo(a)pyrene (BP) to macromolecules in cultured human bronchial mucosa. Bronchial specimens were obtained at either surgy or "immediate" autopsy from patients with and without lung cancer. Grossly normal-appearing pieces of bronchus were cultured in a chemically defined medium, i.e., CMRL 1066 medium containing 1 mug insulin per ml, 0.1 mug beta-retinyl acetate per ml,, 0.1 mug hydrocortisone hemisuccinate per ml, 2 mM L-glutamine, 100 units penicillin G per ml, and 100 mug streptomycin per ml. After 7 days, explant cultures were exposed to [3H]BP, usually for 24 hr, and then binding to total cellular macromolecules was studied by autoradiography, and binding to DNA was measured following isolation of DNA from bronchial mucosal cells. The extent of binding of [3H]BP was dependent on dose of BP, length of exposure to [3H]BP, and temperature. By autoradiography, bronchial epithelial cells bound more [3H]BP than stromal fibroblasts. Both 7,8-benzoflavone and butylated hydroxytoluene appeared to reduce the level of [3H]BP bound to DNA, while nicotine apparently did not alter the level of binding. These studies demonstrate that the bronchial mucosa, an important human cancer target tissue, has the capability to form metabolites of BP which bind to macromolecules including DNA. In addition, 7,8-benzoflavone and butylated hydroxytoluene, both known to alter the microsomal metabolism of BP, reduce the level of [3H]BP bound to DNA.
D001580:Benzopyrenes / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism*; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D046508:Culture Techniques; D004273:DNA, Neoplasm / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors
D001580:Benzopyrenes; D004273:DNA, Neoplasm; D005419:Flavonoids; D002084:Butylated Hydroxytoluene; D009538:Nicotine