Shoukry S, Anderson M W, Glickman B W
Biology Department, York University, Ontario, Canada.
Carcinogenesis. 1993 Jan;14(1):155-7. doi: 10.1093/carcin/14.1.155.
This paper describes the application of the novel nonradioactive technique for studying the sequence selectivity of selected alkylating agents. N-Nitroso-N-methylurea (MNU) and N-methyl-N'-nitro-nitrosoguanidine (MNNG) were chosen from the SN1 group of alkylating agents. Dimethyl sulphate (DMS) was used to represent alkylation profile produced by the SN2 compounds. Results of SN1 compounds indicated that in a run (G)3 the latter two Gs are more susceptible to alkylation than the most 5' G. Moreover, in a GG sequence the 3' G seems to be more alkylated. This effect is more evident when the GG site was preceded by a 5' pyrimidine. These findings suggest that a regio-selective mechanism, rather than the formation of diazonium ions, accounts for DNA alkylation by SN1 compounds. On the other hand, DMS showed preferential alkylation of the 5' end in a (G)3 run. However, at GG sequences no clear preferred site of alkylation could be distinguished. Lack of specificity of SN2 compound would seem to suggest that other factors as well as the primary DNA structure may play a role in determining the extent of alkylation at a certain site.
本文描述了一种用于研究特定烷基化剂序列选择性的新型非放射性技术的应用。从烷基化剂的SN1组中选择了N-亚硝基-N-甲基脲（MNU）和N-甲基-N'-硝基-亚硝基胍（MNNG）。使用硫酸二甲酯（DMS）来代表由SN2化合物产生的烷基化谱。SN1化合物的结果表明，在（G）3序列中，后两个鸟嘌呤（G）比最5'端的鸟嘌呤更容易被烷基化。此外，在GG序列中，3'端的鸟嘌呤似乎被烷基化的程度更高。当GG位点之前是5'嘧啶时，这种效应更为明显。这些发现表明，一种区域选择性机制，而非重氮离子的形成，是SN1化合物导致DNA烷基化的原因。另一方面，DMS在（G）3序列中显示出对5'端的优先烷基化。然而，在GG序列中，无法区分出明显的优先烷基化位点。SN2化合物缺乏特异性似乎表明，除了DNA一级结构外，其他因素可能在决定特定位点的烷基化程度中发挥作用。
