Boyle J M, Durrant L G, Wild C P, Saffhill R, Margison G P
Paterson Laboratories, Christie Hospital & Holt Radium Institute, Manchester, UK.
J Cell Sci Suppl. 1987;6:147-60. doi: 10.1242/jcs.1984.supplement_6.10.
Human cells that lack O6-alkylguanine DNA alkyltransferase (AT) activity can remove O6-butylguanine (O6-nBuG) produced in cellular DNA by exposure to N-n-butyl-N-nitrosourea as determined by radioimmunoassay of enzyme digests of DNA. Fibroblasts from xeroderma pigmentosum (XP) complementation groups A and G that show less than 5% unscheduled DNA synthesis following exposure to UVC failed to remove O6-nBuG. Hence it appears that O6-alkylguanine is repaired in cells that lack AT by a process that is defective in XP cells, presumably nucleotide excision repair. Neither V79 nor V79/79 Chinese hamster cell lines have AT activity and both are able to remove O6-nBuG from DNA. However, only V79/79 is able to remove O6MeG, suggesting some substrate specificity of the excision repair process. Comparison of relative levels of O6-alkylation by N-methyl-, N-ethyl-, N-propyl- and N-n-butyl-nitrosourea indicate that approximately equal levels of O6-alkylation are produced by equitoxic doses of these agents.
缺乏O6-烷基鸟嘌呤DNA烷基转移酶（AT）活性的人类细胞，通过对DNA酶消化物进行放射免疫测定发现，能够去除细胞DNA中因暴露于N-正丁基-N-亚硝基脲而产生的O6-丁基鸟嘌呤（O6-nBuG）。来自着色性干皮病（XP）互补组A和G的成纤维细胞，在暴露于紫外线C（UVC）后显示出少于5%的非预定DNA合成，无法去除O6-nBuG。因此，似乎在缺乏AT的细胞中，O6-烷基鸟嘌呤是通过一种在XP细胞中有缺陷的过程进行修复的，大概是核苷酸切除修复。V79细胞系和V79/79中国仓鼠细胞系都没有AT活性，并且都能够从DNA中去除O6-nBuG。然而，只有V79/79能够去除O6-甲基鸟嘌呤（O6MeG），这表明切除修复过程存在一些底物特异性。对N-甲基-、N-乙基-、N-丙基-和N-正丁基-亚硝基脲引起的O6-烷基化相对水平的比较表明，这些等毒性剂量的试剂产生的O6-烷基化水平大致相等。
