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Interactions of heavy metals with the pulmonary metabolism of (/sup 3/H)benzo(a)pyrene

Journal Article · · Environ. Res.; (United States)
OSTI ID:5995201
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 NiCl/sub 2/, CdCl/sub 2/, and CoCl/sub 2/ on the pulmonary metabolism of (/sup 3/H)benzo(a)pyrene ((/sup 3/H)BAP). Five minutes prior to removing the lungs from a rat, 100 ..mu..l of isotonic sucrose containing 1 ..mu..mole of NiCl/sub 2/, CdCl/sub 2/, or CoCl/sub 2/ was instilled intratracheally. The lungs were placed in the perfusion system and washed free of blood. After 10 min, 5 nmole of (/sup 3/H)BAP dissolved in 100 ..mu..l 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) or analysis by HPLC. Binding of (/sup 3/H)BAP metabolites to lung tissue was also determined. The metabolism of (/sup 3/H)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 NiCl/sub 2/ resulted in a slight inhibition of metabolism. In the presence of CdCl/sub 2/, 20% or 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. CoCl/sub 2/ was without effect on (/sup 3/H)BAP metabolism. In all cases, the extent of covalent binding to lung macromolecules was proportional to the extent of metabolism of the (/sup 3/H)BAP.
Research Organization:
Duke Univ. Medical Center, Durham, NC
OSTI ID:
5995201
Journal Information:
Environ. Res.; (United States), Journal Name: Environ. Res.; (United States) Vol. 34:2; ISSN ENVRA
Country of Publication:
United States
Language:
English

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