Sasaki J C, Arey J, Eastmond D A, Parks K K, Phousongphouang P T, Grosovsky A J
Environmental Toxicology Graduate Program and Air Pollution Research Center, 5419 Boyce Hall, University of California, Riverside, CA 92521, USA.
Mutat Res. 1999 Sep 15;445(1):113-25. doi: 10.1016/s1383-5718(99)00118-7.
2-Nitronaphthalene (2NN) has been identified as a mutagenic atmospheric reaction product of naphthalene in the Ames bacterial reversion assay. Recent experiments have shown this nitroarene to be genotoxic in a human lymphoblastoid cell line (MCL-5) transfected with plasmids encoding epoxide hydrolase and four cytochrome P450 monooxygenase activities. The present study investigated the genotoxicity of 2NN in two related human B-lymphoblastoid cell lines, h1A1v2 containing a single P450 isozyme (cytochrome P450 1A1) and L3 cells which are isogenic with MCL-5 cells and are distinguished only by the absence of transfected plasmids. The results indicate that 2NN-induced mutagenesis at the heterozygous thymidine kinase (tk) locus was dependent on metabolic activities provided by the transfected plasmids in MCL-5; no significant induction of mutants was observed in L3 cells studied in parallel. A similar induction of mutation was observed in h1A1v2 and MCL-5 cell lines at the tk locus and no induction was observed at the hemizygous hypoxanthine phosphoribosyl transferase (hprt) locus. The induction of mutations in h1A1v2 cells suggests that cytochrome P450 1A1 alone can activate 2NN to a mutagenic species, however, this interpretation may be confounded by differences between the h1A1v2 and MCL-5 cell lines. The observed genotoxic activity induced by 2NN prompted testing of the amino analogue, beta-naphthylamine (betaNA), to investigate potential similarities in the metabolic activation pathways of the two compounds. The negative response of betaNA in all cell lines suggests that 2NN and betaNA are not activated in these human cells by similar metabolic pathways.
在艾姆斯细菌回复突变试验中，2-硝基萘（2NN）已被确定为萘的一种致突变大气反应产物。最近的实验表明，这种硝基芳烃在转染了编码环氧化物水解酶和四种细胞色素P450单加氧酶活性的质粒的人淋巴母细胞系（MCL-5）中具有遗传毒性。本研究调查了2NN在两种相关的人B淋巴母细胞系中的遗传毒性，一种是含有单一P450同工酶（细胞色素P450 1A1）的h1A1v2细胞系，另一种是与MCL-5细胞同基因的L3细胞系，L3细胞系与MCL-5细胞的区别仅在于未转染质粒。结果表明，2NN在杂合胸苷激酶（tk）位点诱导的突变依赖于MCL-5中转染质粒提供的代谢活性；在平行研究的L3细胞中未观察到突变体的显著诱导。在h1A1v2和MCL-5细胞系的tk位点观察到类似的突变诱导，而在半合子次黄嘌呤磷酸核糖基转移酶（hprt）位点未观察到诱导。h1A1v2细胞中突变的诱导表明，仅细胞色素P450 1A1就能将2NN激活为诱变剂，然而，这种解释可能因h1A1v2和MCL-5细胞系之间的差异而混淆。2NN诱导的遗传毒性活性促使对氨基类似物β-萘胺（βNA）进行测试，以研究这两种化合物代谢激活途径的潜在相似性。βNA在所有细胞系中的阴性反应表明，2NN和βNA在这些人细胞中不是通过相似的代谢途径被激活的。
