Evaluation of the Potential Health Effects of the Atmospheric Reaction Products211 of Polycyclic Aromatic Hydrocarbons

摘要

The authors utilized human cell assays to evaluate the genotoxicity of211u001enaphthalene, phenanthrene, and their atmospheric reaction products 1-211u001enitronaphthalene, 2-nitronaphthalene (2NN), 2-hydroxy-2NN, 2-hydroy-1-211u001enitronaphthalene, 1,4-naphthoquinone, and 2-nitrodibenzopyranone (2NDBP). 211u001eSimulate atmospheric reaction products of naphthalene were also generated, 211u001efractionated, and tested for genotoxic effects using the human B-lymphoblastoid 211u001ecell line, MCL-5 (which expresses several transfected P450 and epoxide hydrolase 211u001egenes) and the CREST modified micronucleus assay. 2NN and 2NDBP had greater 211u001emutagentic potency than their parent compounds, and both compounds induced 211u001esignificant increases in mutation frequency at tk but not hprt. These findings 211u001esuggest a mechanistic difference in human cell response as compared with that of 211u001ebacteria and emphasize the need to consider atmospheric reaction products of 211u001epolycyclic aromatic hydrocarbons (PAHs) in assessing genotoxicity of air 211u001epollutants. The authors also used three related cell lines with multiple (MCL-5), 211u001esingle (AHH-1 1A1), or not (L3) transfected cytochrome P450 genes to investigate 211u001ewhether transfected cytochrome P450 monooygenase activities were required to 211u001eactivate 2NN and 2NDBP to genotoxic species. 2NN and 2NDBP were not activated to 211u001egenotoxic species through nitroreduction pathways. Mutagenicity induced at the tk 211u001elocus depended on oxidative metabolism, provided by transfected cytochrome P450 211u001eenzymes. The negative response indicates that 2NN and (beta)NA were not activated 211u001eby similar metabolic pathways and suggests that the genotoxicity of nitro-PAHs in 211u001ehuman cells requires oxidative metabolism.