Serebryanyi A M, Sal'nikova L E, Bakhitova L M
Institute of Chemical Physics, U.S.S.R. Academy of Sciences, Moscow.
Mutat Res. 1990 Aug;231(2):195-203. doi: 10.1016/0027-5107(90)90026-z.
Study of the mutagenic action of methyl nitrosourea (MNU) on the CHO-AT3-2 Chinese hamster cell at 2 regimes of cell treatment (a short-term regime and prolonged 1-h treatment) revealed that increase in the duration of treatment enhanced both cell lethality and clastogenic and mutagenic effects at the TK locus and did not influence the mutation frequency at the OUAr locus. On the basis of kinetic considerations it can be concluded that the base-pair substitution-type mutants (e.g., OUAr) appear as a result of DNA alkylation and the mutants at loci with a wide spectrum of registered mutants (the TK locus) are related to a greater extent to the carbamoylating activity of MNU. This conclusion is confirmed by measurements of the effects of sequential treatment with MNU (7 min) and KNCO (1 h). A synergistic increase in lethality, clastogenicity and mutagenicity at the TK locus was found in experiments with the combined treatment of cells with ethyl methanesulfonate (EMS) and KNCO. Besides, pretreatment of cells with potassium cyanate and subsequent exposure to MNU, EMS and benzopyrene (BP) produced synergistic effects in all the tests: lethality, clastogenicity and mutation frequency at the OUAr and TK loci. Posttreatment of cells with KNCO also led to a synergistic increase in the effects of MNU, EMS and BP treatment in several tests, but not in the OUAr locus. The possible mechanism and levels of interactions between alkylation and carbamoylation and the possibility that potassium cyanate causes supramolecular lesions are discussed.
对甲基亚硝基脲（MNU）在两种细胞处理方式（短期处理和延长1小时处理）下对中国仓鼠CHO - AT3 - 2细胞的诱变作用研究表明，处理时间延长会增强细胞致死率以及在胸苷激酶（TK）位点的断裂和诱变效应，而对次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（OUAr）位点的突变频率没有影响。基于动力学考虑可以得出结论，碱基对替换型突变体（如OUAr）是DNA烷基化的结果，而在具有多种已记录突变体的位点（TK位点）的突变体在更大程度上与MNU的氨甲酰化活性有关。用MNU（7分钟）和氰酸钾（KNCO）（1小时）进行顺序处理的效果测量证实了这一结论。在用甲磺酸乙酯（EMS）和KNCO联合处理细胞的实验中，发现TK位点的致死率、断裂性和诱变性有协同增加。此外，用氰酸钾预处理细胞，随后暴露于MNU、EMS和苯并芘（BP），在所有测试中都产生了协同效应：OUAr和TK位点的致死率、断裂性和突变频率。用KNCO对细胞进行后处理在一些测试中也导致MNU、EMS和BP处理效果的协同增加，但在OUAr位点没有。讨论了烷基化和氨甲酰化之间相互作用的可能机制和水平以及氰酸钾导致超分子损伤 的可能性。
