Metabolic activation of nitropyrenes and diesel-particulate extracts. Research report Aug 83-Jul 88

The study compared DNA adducts formed between 1-nitropyrene (1-NP), 1,3-dinitropyrene(1,3-DNP), 1,6-dinitropyrene(1,6-DNP), or 1,8-dinitropyrene(1,8-DNP) and cellular DNA in various systems (including human bronchial segments, rabbit lung and trachea, and mouse embryo fibroblast C3H/10T1/2 cells) with those formed in Salmonella typhimurium. The study administered radiolabeled nitropyrenes, and isolated and digested the modified DNA. By HPLC, elution times of the radioactive adducts were compared with synthetic standards. Metabolism of 1-NP was most evident in the human bronchial tissue. Little metabolism occurred in duodenal and colonic samples. Mouse C3H/10T1/2 embryo fibroblasts showed no detectable metabolism of, DNA adduct formation with, or transformation by 1-NP. DNA adducts occurred in cells exposed to 1,8-DNP and traces of adducts formed with either 1,3-DNP or 1,6-DNP. DNA adducts after treatment with (4,5,9,10-(3)H)-1-NP in rabbit tracheal samples showed that 2 to 15 percent could be accounted for as the C-8 adduct. The study used antibodies to detect 1-NP adducts in S. typhimurium TA 1538. They detected adducts in the livers of female, but not male, rats treated with 1-NP. The study found that these antisera showed cross-reactivity with other DNA adducts. The study used (32)P-postlabeling to analyze DNA samples from animals exposed for 30 months to high levels of more » diesel engine emissions. This exposure resulted in elevated levels of DNA adducts. « less