Interactions of heavy metals with the pulmonary metabolism of [3H]benzo[a]pyrene.
To test the hypothesis that the inhalation of heavy metal aerosols from polluted air or cigarette smoke could alter the metabolism of polycyclic aromatic hydrocarbons, isolated, ventilated, and perfused rat lungs were used to study the effects of NiCl2, CdCl2, and CoCl2 on the pulmonary metabolism of [3H]benzo[a]pyrene [( 3H]BAP). Five minutes prior to removing the lungs from a rat, 100 microliter of isotonic sucrose containing 1 mumole of NiCl2, CdCl2, or CoCl2 was instilled intratracheally. The lungs were placed in the perfusion system and washed free of blood. After 10 min, 5 nmole of [3H]BAP dissolved in 100 microliter of dimethylsulfoxide was introduced in the arterial circulation. After 45 min, the lungs were homogenized and the homogenates and perfusates were extracted with ethyl acetate:acetone (2:1, v/v) for analysis by HPLC. Binding of [3H]BAP metabolites to lung tissue was also determined. The metabolism of [3H]BAP was found to be inducible by pretreatment of rats with beta-naphthoflavone (80 mg/kg) and to be inhibited by the inclusion of metyrapone (1.0 mM) or indomethacin (0.1 mM) in the perfusate. Instillation of NiCl2 resulted in a slight inhibition of metabolism. In the presence of CdCl2, 20% more of the parent compound was metabolized compared to sucrose-treated controls, but the fraction of organic solvent extractable metabolites increased to 213% of controls. CoCl2 was without effect on [3H]BAP metabolism. In all cases, the extent of covalent binding to lung macromolecules was proportional to the extent of metabolism of the [3H]BAP. Since heavy metals and polycyclic aromatic hydrocarbons coexist in the same atmospheric aerosols, heavy metal exposure from polluted urban or occupational air or cigarette smoking may have profound effects upon the bioactivity of a common organic carcinogen.
D000818:Animals; D001564:Benzo(a)pyrene; D001571:Benzoflavones / Q000494:pharmacology; D001580:Benzopyrenes / Q000378:metabolism*; D001711:Biotransformation; D002104:Cadmium / Q000494:pharmacology*; D019256:Cadmium Chloride; D002851:Chromatography, High Pressure Liquid; D003035:Cobalt / Q000494:pharmacology*; D004347:Drug Interactions; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D001580:Benzopyrenes; D002104:Cadmium; D014316:Tritium; D001564:Benzo(a)pyrene; D003035:Cobalt; D019324:beta-Naphthoflavone; C022838:nickel chloride; D009532:Nickel; C018021:cobaltous chloride; D019256:Cadmium Chloride; D007213:Indomethacin; D008797:Metyrapone