Scheepers P T, Theuws J L, Bos R P
Department of Toxicology, University of Nijmegen, The Netherlands.
Mutat Res. 1991 Aug;260(4):393-9. doi: 10.1016/0165-1218(91)90025-h.
1-Nitropyrene (1-NP) and 2-nitrofluorene (2-NF), two of the most abundant nitro-substituted polycyclic aromatic hydrocarbons (nitro-PAH) present in combustion products such as diesel engine exhaust, were administered intraperitoneally to rats at a dose of 5 mg per animal. Urine samples, 1-NP and 2-NF were tested in the Ames assay using the newly developed Salmonella typhimurium strains YG1012 and YG1024 (overproducing O-acetyltransferase) and their parent strains TA1538 and TA98. In urine, collected over 3 periods of 24 h after administration, most of the mutagens appeared during the first 24 h. The mutagenicity was found to be a factor 2-30 higher in the YG strains when compared to the TA strains. Addition of S9 mix and rat liver cytosol both with and without beta-glucuronidase increased the mutagenicity of urine samples from 1-NP-treated rats. Addition of beta-glucuronidase revealed that a considerable part of the mutagenic metabolites of 1-NP and 2-NF were excreted as glucuronide conjugates. The increase in mutagenicity of urine samples from 2-NF-treated rats after the addition of rat liver cytosol referred to N,O-acyl transfer as a step in activating 2-NF to strong mutagens. The high sensitivity of the YG tester strains indicated that these strains might be used to explore environments where people are exposed to nitro-PAH, such as work places with diesel emission sources.
1-硝基芘(1-NP)和2-硝基芴(2-NF)是柴油发动机尾气等燃烧产物中最常见的两种硝基取代多环芳烃(硝基-PAH),以每只动物5毫克的剂量腹腔注射给大鼠。使用新开发的鼠伤寒沙门氏菌菌株YG1012和YG1024(过量产生O-乙酰转移酶)及其亲本菌株TA1538和TA98,对尿液样本、1-NP和2-NF进行艾姆斯试验。在给药后24小时的3个时间段内收集的尿液中,大多数诱变剂在最初24小时内出现。与TA菌株相比,发现YG菌株的诱变性高2至30倍。添加S9混合物以及添加和不添加β-葡萄糖醛酸酶的大鼠肝细胞溶胶均可增加1-NP处理大鼠尿液样本的诱变性。添加β-葡萄糖醛酸酶表明,1-NP和2-NF的相当一部分诱变代谢物以葡萄糖醛酸共轭物的形式排泄。添加大鼠肝细胞溶胶后,2-NF处理大鼠尿液样本的诱变性增加,这表明N,O-酰基转移是将2-NF激活为强诱变剂的一个步骤。YG测试菌株的高灵敏度表明,这些菌株可用于探索人们接触硝基-PAH的环境,例如有柴油排放源的工作场所。