Connell J R, Medcalf A S
Carcinogenesis. 1982;3(4):385-90. doi: 10.1093/carcin/3.4.385.
Chinese hamster cells (V79) were treated, either as exponentially proliferating cultures or under conditions where they were density-inhibited, with various doses of the potent carcinogen N-methyl-N-nitrosourea (MNU) or the relatively weak carcinogen dimethylsulphate (DMS). The colony forming ability of these cells and the induced frequencies of sister chromatid exchanges (SCEs) and chromosomal aberrations were assayed. Following the exposure of density-inhibited cells to radio-labelled methylating agents (labelled in the methyl group) these phenomena were related to the levels of 7-methylguanine (7-meGua), O6-methylguanine (O6-meGua) and 3-methyladenine (3-me-Ade) in the DNA. At equitoxic doses MNU and DMS induced similar frequencies of SCEs and chromosomal aberrations. Since, at equitoxic doses, MNU produces approximately 20 times more O6-meGua in V79 cell DNA than does DMS, this indicates that the formation of O6-meGua in DNA is not a major cause of SCEs and chromosomal aberrations. DMS-induced SCEs may be mediated via the production of both 3-meAde and 7-meGua in the DNA; these two methylated purines may also be responsible for MNU-induced SCEs. Therefore, no one specific methylated purine was identified as being solely accountable for the formation of SCEs. Also, the repair of lesions in the DNA of non-replicating V79 cells leads to a reduction in the SCE frequency on their subsequent release from the density-inhibited state, suggesting that repair is not intimately responsible for their formation. No association was discernable between chromosomal aberrations and any of the three methylated purines studied.
将中国仓鼠细胞（V79）作为指数增殖培养物，或在密度抑制条件下，用不同剂量的强效致癌物N-甲基-N-亚硝基脲（MNU）或相对较弱的致癌物硫酸二甲酯（DMS）进行处理。测定这些细胞的集落形成能力以及诱导的姐妹染色单体交换（SCE）频率和染色体畸变。在将密度抑制的细胞暴露于放射性标记的甲基化剂（甲基标记）后，这些现象与DNA中7-甲基鸟嘌呤（7-meGua）、O6-甲基鸟嘌呤（O6-meGua）和3-甲基腺嘌呤（3-me-Ade）的水平相关。在等毒性剂量下，MNU和DMS诱导的SCE和染色体畸变频率相似。由于在等毒性剂量下，MNU在V79细胞DNA中产生的O6-meGua比DMS多约20倍，这表明DNA中O6-meGua的形成不是SCE和染色体畸变的主要原因。DMS诱导的SCE可能通过DNA中3-meAde和7-meGua的产生介导；这两种甲基化嘌呤也可能是MNU诱导的SCE的原因。因此，没有一种特定的甲基化嘌呤被确定为是SCE形成的唯一原因。此外，非复制性V79细胞DNA损伤的修复导致其随后从密度抑制状态释放时SCE频率降低，这表明修复与它们的形成没有密切关系。在所研究的三种甲基化嘌呤与染色体畸变之间没有明显的关联。
