The activation of mutagens in diesel particle extract with rat liver S9 enzymes.
Reductive activation of nitroaromatic compounds by bacterial enzymes contributes to the direct-acting mutagenicity of diesel particle extracts in the Salmonella mutation assay. In this study, the ability of mammalian enzymes to activate diesel particle extract was investigated with a rat liver S9 preparation using the nitroreductase-deficient strain TA98NR to detect active metabolic products. The use of diesel particle extract at concentrations greater than 50 micrograms per plate inhibited S9 enzyme activations in the mutation assay. In addition, the S9 preparation without NADPH present decreased the residual direct-acting mutagenicity of the particle extract. Activation by S9 enzymes of mutagens in diesel particle extract was evident as a difference in activity between assays with and without NADPH. 1-Nitropyrene, a nitroarene identified in diesel particle extracts, was also activated by NADPH-dependent S9 enzymes. S9 activation of both the particle extract and 1-nitropyrene was detected only when using much lower S9 concentrations than conventionally applied in the Salmonella/S9 assay. S9 enzyme activation of 1-nitropyrene is not merely a consequence of forming a mutagenic amine since 1-aminopyrene was less mutagenic than 1-nitropyrene in these assays. The NADPH-dependent activation of 1-nitropyrene is located in the microsomal fraction of the S9 preparation. However, activation of the diesel particle extract was more evident with the cytosol than with the microsomal fraction, demonstrating the involvement of yet other enzyme systems and extract components.
D000393:Air Pollutants; D000818:Animals; D001711:Biotransformation; D005648:Fuel Oils; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010578:Petroleum; D011083:Polycyclic Compounds / Q000378:metabolism*; D011721:Pyrenes / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000235:genetics; D001335:Vehicle Emissions
D000393:Air Pollutants; D005648:Fuel Oils; D009153:Mutagens; D010578:Petroleum; D011083:Polycyclic Compounds; D011721:Pyrenes; D001335:Vehicle Emissions; D009249:NADP; C032668:1-nitropyrene