Grunberg S M, Haseltine W A
Proc Natl Acad Sci U S A. 1980 Nov;77(11):6546-50. doi: 10.1073/pnas.77.11.6546.
A highly reiterated sequence of human DNA was used to determine the sites of modification of DNA caused by the anti-tumor drug methylbis(2-chloroethyl)amine (HN2, mechlorethamine, nitrogen mustard) upon treatment of cells in culture and of purified DNA. The lengths of the breakage products of the DNA treated with HN2 were compared to the lengths of DNA scission products produced by chemical reactions used for DNA sequence determination. HN2 was found to create alkali-labile lesions at positions of guanine. The distribution of the guanine modifications was the same for DNA extracted from cells treated with HN2 and for purified DNA treated with HN2. However, the extent of damage was at least 2-fold greater when purified DNA was used as the substrate. Several nitrogen mustard analogues also produced alkali-labile lesions at positions of guanine.
一段高度重复的人类DNA序列被用于确定抗肿瘤药物甲基双（2-氯乙基）胺（HN2，氮芥，盐酸氮芥）在处理培养细胞和纯化DNA时所引起的DNA修饰位点。将经HN2处理的DNA断裂产物的长度与用于DNA序列测定的化学反应所产生的DNA切割产物的长度进行比较。发现HN2在鸟嘌呤位置产生碱不稳定损伤。从经HN2处理的细胞中提取的DNA以及经HN2处理的纯化DNA中，鸟嘌呤修饰的分布是相同的。然而，当使用纯化DNA作为底物时，损伤程度至少大2倍。几种氮芥类似物也在鸟嘌呤位置产生碱不稳定损伤。
