Bresler S E, Kalinin V L, Kuznetsova L V
Genetika. 1984 Jun;20(6):933-42.
The lethal and mutagenic effects of 7 alkylating agents: N-nitroso-N-methylurea (NMU), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), methyl methanesulfonate (MMS), ethyl methanesulfonate (EMS), nitrogen mustard (HN2), mitomycin C (MC), bifunctional acridine mustard (AM)--and of cyanate (KNCO) on heat inducible lambda cI857 prophage were studied. After treatment of lysogenic cells with mutagens, prophage was heat-induced either immediately or after 90 min incubation in nutrient broth and c mutants forming clear plaques at 32 degrees C were scored. NMU (0.02 M) when immediately induced with heat, induces c mutants very efficiently (maximal yield 10%) not only in the wild-type cells but also in repair-deficient mutants recA13, lexA102, uvrA6 umuC36, recF143, xthA9, polA1, uvrD3 and uvrD502. These data show that NMU-induced mutations are fixed as replication errors due to mispairing modified bases. After delayed heat induction, the prophage survival enhances and the frequency of c mutations declines considerably in host cells of all repair genotypes tested. Carbamoylation is not involved in the mutagenic action of NMU, because KNCO (0.02 M) has a very slight lethal effect and does not induce mutations. MNNG (100 micrograms/ml) and EMS (0.1 M) also induce mutations by replicative mechanism, because maximal yield of c mutations does not depend on RecA+ and is about 15 and 2%, respectively. MMS is a mutagen of the repair type, since its mutagenic action is suppressed by recA mutation of the host. NH2 only inactivates prophage, but does not induce mutations. MC (50 micrograms/ml) and AM (150 micrograms/ml) induce mutations rather inefficiently (the maximal yield 0.1 and 0.3%, respectively) both in recA+ and recA- hosts. The mutagenic action of these agents is probably due to intercalation.
研究了7种烷化剂：N-亚硝基-N-甲基脲（NMU）、N-甲基-N'-硝基-N-亚硝基胍（MNNG）、甲磺酸甲酯（MMS）、乙磺酸甲酯（EMS）、氮芥（HN2）、丝裂霉素C（MC）、双功能吖啶芥（AM）以及氰酸盐（KNCO）对热诱导的λcI857原噬菌体的致死和诱变作用。用诱变剂处理溶源细胞后，原噬菌体立即或在营养肉汤中孵育90分钟后进行热诱导，并对在32℃形成清晰噬菌斑的c突变体进行计数。NMU（0.02M）在热诱导后立即诱导c突变体的效率非常高（最大产量为10%），不仅在野生型细胞中如此，在修复缺陷型突变体recA13、lexA102、uvrA6、umuC36、recF143、xthA9、polA1、uvrD3和uvrD502中也是如此。这些数据表明，NMU诱导的突变是由于错配修饰碱基而作为复制错误固定下来的。延迟热诱导后，在所测试的所有修复基因型的宿主细胞中，原噬菌体存活率提高，c突变频率显著下降。氨甲酰化不参与NMU的诱变作用，因为KNCO（0.02M）具有非常轻微的致死作用且不诱导突变。MNNG（100微克/毫升）和EMS（0.1M）也通过复制机制诱导突变，因为c突变的最大产量不依赖于RecA+，分别约为15%和2%。MMS是一种修复型诱变剂，因为其诱变作用被宿主的recA突变所抑制。HN2仅使原噬菌体失活，但不诱导突变。MC（50微克/毫升）和AM（150微克/毫升）在recA+和recA-宿主中诱导突变的效率都相当低（最大产量分别为0.1%和0.3%）。这些试剂的诱变作用可能是由于嵌入作用。
