Busby W F, Smith H, Bishop W W, Thilly W G
Division of Toxicology, Massachusetts Institute of Technology, Cambridge 02139.
Mutat Res. 1994 Oct;322(4):221-32. doi: 10.1016/0165-1218(94)90098-1.
Nitropyrenes are a group of widespread environmental pollutants, some of which are highly potent as bacterial and mammalian cell mutagens and as animal carcinogens. A quantitative bacterial forward mutation assay, based on resistance to 8-azaguanine (8-AG) in Salmonella typhimurium TM677, was employed as an alternative to reversion assays to reexamine the mutagenicity of 1-, 2-, and 4-nitropyrene (1-, 2-, and 4-NP) and 1,3-, 1,6-, and 1,8-dinitropyrene (1,3-, 1,6-, and 1,8-DNP) in the presence and absence of rat liver postmitochondrial supernatant (PMS). The major finding is that 2-NP, reported as a potent mutagen in the absence of PMS in bacterial reversion assays, was inactive in the absence of PMS in this assay. However, 2-NP was mutagenic in the presence of PMS. The implications of this observation with respect to sample purity and the metabolism of 2-NP are discussed. Without PMS the following minimum detectable mutagen concentration (MDMC) potency series expressed as nmol/ml was obtained: 1,8-DNP (0.5 x 10(-3)), 1,6-DNP (1.2 x 10(-3)), 1,3-DNP (2.3 x 10(-3)), 4-NP (0.2), 1-NP (0.2), 2-NP (> 1200), pyrene (> 1500). With PMS the potency series was: 1,6-DNP (0.7), 1,8-DNP (2.1), 4-NP (2.2), 2-NP (2.6), 1,3-DNP (3.7), 1-NP (4.6), pyrene (> 1500). With the exception of 2-NP, all the nitropyrenes were more mutagenic without PMS than with PMS. The greatest difference was observed with the dinitropyrenes, which were three orders of magnitude less potent in the presence of PMS. Pyrene, often reported as a bacterial mutagen in the presence of PMS, was nonmutagenic in this assay when a purified sample was tested.
硝基芘是一类广泛存在的环境污染物，其中一些作为细菌和哺乳动物细胞诱变剂以及动物致癌物具有很强的活性。采用一种基于鼠伤寒沙门氏菌TM677对8 - 氮杂鸟嘌呤（8 - AG）抗性的定量细菌正向突变试验，替代回复突变试验，重新检测1 - 、2 - 和4 - 硝基芘（1 - 、2 - 和4 - NP）以及1,3 - 、1,6 - 和1,8 - 二硝基芘（1,3 - 、1,6 - 和1,8 - DNP）在有和没有大鼠肝脏线粒体后上清液（PMS）存在时的诱变性。主要发现是，在细菌回复突变试验中，2 - NP在没有PMS时被报告为强效诱变剂，但在本试验中，在没有PMS时它没有活性。然而，2 - NP在有PMS时具有诱变性。讨论了这一观察结果对样品纯度和2 - NP代谢的影响。在没有PMS的情况下，获得了以下以nmol/ml表示的最低可检测诱变剂浓度（MDMC）效力序列：1,8 - DNP（0.5×10⁻³）、1,6 - DNP（1.2×10⁻³）、1,3 - DNP（（2.3×10⁻³）、4 - NP（0.2）、1 - NP（0.2）、2 - NP（>1200）、芘（>1500）。在有PMS的情况下，效力序列为：1,6 - DNP（0.7）、1,8 - DNP（2.1）、4 - NP（2.2）、2 - NP（2.6）、1,3 - DNP（3.7）、1 - NP（4.6）、芘（>1500）。除2 - NP外，所有硝基芘在没有PMS时比有PMS时更具诱变性。在二硝基芘中观察到最大差异，它们在有PMS时的效力低三个数量级。芘在有PMS时通常被报告为细菌诱变剂，但在本试验中，当测试纯化样品时它没有诱变性。
