Lambert I B, Carroll C, Laycock N, Koziarz J, Lawford I, Duval L, Turner G, Booth R, Douville S, Whiteway J, Nokhbeh M R
Biology Department, Carleton University, 1125 Colonel By Drive, Ont., K1S 5B6, Ottawa, Canada.
Mutat Res. 2001 Dec 12;484(1-2):19-48. doi: 10.1016/s0027-5107(01)00234-2.
We have characterized 202 lacI(-) mutations, and 158 dominant lacI(-d) mutations following treatment of Escherichia coli strains NR6112 and EE125 with 1-nitroso-6-nitropyrene (1,6-NONP), an activated metabolite of the carcinogen 1,6-dinitropyrene. In all, 91% of the induced point mutations occurred at G:C residues. The -(G:C) frameshifts were the dominant mutational class in the lacI(-) collections of both NR6112 and EE125, and in the lacI(-d) collection of NR6112. Frameshift mutations occurred preferentially in runs of guanine residues, and their frequency increased with the length of the reiterated sequence. In strain EE125, which contained the plasmid pKM101, there was a marked stimulation in the frequency of base substitution mutations that was particularly apparent in the lacI(-d) collection. This study completes a comprehensive analysis of 1194 lacI(-) and 348 lacI(-d) mutations induced by either 1,6-NONP or its positional isomer 1-nitroso-8-nitropyrene (1,8-NONP) in strains of E. coli that differ with regard to their ability to carry out nucleotide excision repair and/or their ability to express the translesion synthesis DNA polymerase RI (MucAB) encoded by plasmid pKM101. Among the mutations are 763 frameshift mutations, 367 base substitutions and 47 deletions; these mutations have been characterized at more than 300 distinct sites in the lacI gene. Our studies provide detailed insight into the DNA sequence alterations and mutational mechanisms associated with dinitropyrene mutagenesis. We review the mutational spectra, and discuss cellular lesion repair or tolerance mechanisms that modulate the observed mutational specificity.
我们对用致癌物1,6 - 二硝基芘的活性代谢物1 - 亚硝基 - 6 - 硝基芘（1,6 - NONP）处理大肠杆菌菌株NR6112和EE125后产生的202个lacI(-)突变以及158个显性lacI(-d)突变进行了特征分析。总共，91%的诱导点突变发生在G:C残基处。-(G:C)移码突变是NR6112和EE125的lacI(-)集合以及NR6112的lacI(-d)集合中的主要突变类型。移码突变优先发生在鸟嘌呤残基序列中，其频率随着重复序列长度的增加而增加。在含有质粒pKM101的EE125菌株中，碱基替换突变的频率有显著增加，这在lacI(-d)集合中尤为明显。本研究完成了对大肠杆菌菌株中由1,6 - NONP或其位置异构体1 - 亚硝基 - 8 - 硝基芘（1,8 - NONP）诱导产生的1194个lacI(-)和348个lacI(-d)突变的全面分析，这些大肠杆菌菌株在进行核苷酸切除修复的能力和/或表达由质粒pKM101编码的跨损伤合成DNA聚合酶RI（MucAB）的能力方面存在差异。这些突变包括763个移码突变、367个碱基替换和47个缺失；这些突变已在lacI基因的300多个不同位点进行了特征分析。我们的研究为与二硝基芘诱变相关的DNA序列改变和突变机制提供了详细的见解。我们回顾了突变谱，并讨论了调节观察到的突变特异性的细胞损伤修复或耐受机制。
