Snow E T, Singh J, Koenig K L, Solomon J J
Nelson Institute of Environmental Medicine, New York University Medical Center, Tuxedo 10987.
Environ Mol Mutagen. 1994;23(4):274-80. doi: 10.1002/em.2850230403.
Propylene oxide (PO) is a widely used industrial reagent which is mutagenic and carcinogenic. We have recently shown that a variety of aliphatic epoxides, including propylene oxide, can react with DNA to form hydroxyalkyl adducts at N-3 of cytosine which rapidly undergo hydrolytic deamination to produce uracil adducts. These 3-hydroxyalkyl uracil adducts are stable in DNA and are postulated to be an important class of potentially mutagenic lesions. Mutagenesis at cytosine residues due to PO modification of single-stranded M13mp2/C141 DNA was studied by transfection of modified DNA into SOS and non-SOS induced E. coli host cells. Mutations of the proline (CCC) codon at C141 which result in reversion of the lacZ phenotype (blue plaques) were scored. It was found that PO treatment of single-stranded DNA results in dose-dependent mutagenesis that is highly SOS dependent. The spectrum of base-substitution mutations found at this site differed when PO-modified DNA was transfected into E. coli with different DNA repair backgrounds. These results indicate that propylene oxide induced DNA adducts at template cytosine residues are mutagenic in E. coli and that this mutagenesis is greatly increased by SOS processing. They also show that these lesions may be repaired by one or more mechanisms.
环氧丙烷（PO）是一种广泛使用的工业试剂，具有致突变性和致癌性。我们最近发现，包括环氧丙烷在内的多种脂肪族环氧化物可与DNA反应，在胞嘧啶的N-3位形成羟烷基加合物，这些加合物会迅速发生水解脱氨反应生成尿嘧啶加合物。这些3-羟烷基尿嘧啶加合物在DNA中稳定存在，并被认为是一类重要的潜在致突变损伤。通过将修饰后的DNA转染到SOS诱导型和非SOS诱导型大肠杆菌宿主细胞中，研究了单链M13mp2/C141 DNA经PO修饰后胞嘧啶残基处的诱变情况。对C141处脯氨酸（CCC）密码子的突变进行评分，这些突变会导致lacZ表型（蓝色噬菌斑）的回复突变。结果发现，PO处理单链DNA会导致剂量依赖性诱变，且高度依赖SOS。当将PO修饰的DNA转染到具有不同DNA修复背景的大肠杆菌中时，在该位点发现的碱基替换突变谱有所不同。这些结果表明，环氧丙烷在模板胞嘧啶残基处诱导的DNA加合物在大肠杆菌中具有致突变性，并且这种诱变在SOS处理下会大大增加。它们还表明，这些损伤可能通过一种或多种机制进行修复。
