Metabolism of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in cultured human bronchus and pancreatic duct.

Abstract

Summary The metabolism of two carcinogenic polynuclear aromatic hydrocarbons, benzo[ a ]pyrene (BP) and 7,12-dimethylbenz[ a ]anthracene, was studied in explants of human pancreatic duct and bronchus cultured in a chemically defined medium. In cultured human bronchial mucosa, activity of aryl hydrocarbon hydroxylase was inducible by both benz[ a ]anthracene and BP. Prior exposure of the bronchial explants to benz[ a ]anthracene altered the qualitative features of the metabolite profile of BP as analyzed by high-pressure liquid chromatography. The metabolite profiles of BP produced by normal-appearing bronchi from patients with lung cancer were also compared with those from patients without lung cancer. The profiles were similar except for an observed higher percentage of organic solvent-extractable metabolites formed by bronchi from the noncancer patients that eluted from the column as a single peak. This peak cochromatographed with both the 9,10-diol and a triol of BP. 7,12-Dimethylbenz[ a ]anthracene was bound to the DNA of cultured human bronchial cells at higher levels than was BP. Binding of 7,12-dimethylbenz[ a ]anthracene to DNA in human pancreatic duct was consistently less than that in cultured bronchi in the 5 patients studied. Human pancreatic duct and bronchus have the capacity to activate polynuclear aromatic hydrocarbons into metabolic intermediates that bind to DNA and, presumably, into ultimate carcinogens.