Mutagenicity of benzo(a)pyrene metabolites generated on the isolated perfused lung following particulate exposure

The isolated perfused rabbit lung (IPL) is being used to study the effects of particulate exposure on the pulmonary metabolism of benzo(a)pyrene (BaP). Pasturealla-free New Zealand white rabbits were treated intraperitoneally with BaP prior to kill. The isolated lungs were then administered either 14C-labeled BaP alone or BaP plus Fe2O3 or fly ash by intratracheal injection. Rates of appearance of BaP metabolites in the perfusing blood were determined. The extent of metabolism, distribution of metabolites, and types of metabolites produced were quantified for various lung tissue types by high-performance liquid chromatography and liquid scintillation spectrometry. Procedures were developed to apply the Salmonella/microsome test in the assay of mutagenicity of lung tissue and blood extracts as an indicator of their biologic activity. With few exceptions, blood extracts from IPL receiving BaP only were not mutagenic. Lung, trachea-bronchi, and macrophage extracts, by contrast, were mutagenic. A part of this activity could be attributed to BaP metabolites rather than to parent compound remaining in extracts. When lungs were exposed to Fe2O3 or to fly ash, only macrophage extracts were consistently mutagenic. This activity was due to significant amounts of unmetabolized BaP.