Mirzayans R, Waters R
Carcinogenesis. 1981;2(12):1359-62. doi: 10.1093/carcin/2.12.1359.
Normal human or excision deficient xeroderma pigmentosum (XP) fibroblasts were exposed to either the potent carcinogen 4-nitroquinoline 1-oxide (4NQO) or the weaker acting 3 methyl derivative of this compound. The inhibition of cell growth, DNA damage and DNA repair were then monitored in these cells. The data indicate that the modification of 4NQO by methylation actually changes the type and amount of DNA damage induced by this carcinogen. More specifically, the methylation of 4NQO at the three position prevented the formation of 4NQO induced DNA adducts manifesting themselves as alkaline stable lesions whose repair was cytosine arabinoside inhibitable in normal cells, but defective in excision deficient XP cells. Alkaline labile lesions induced by 4NQO which are repairable in the above XP cells were still induced by the 3 methyl derivative but a lower frequency on an equimolar basis.
将正常人成纤维细胞或切除缺陷型着色性干皮病（XP）成纤维细胞暴露于强效致癌物4-硝基喹啉-1-氧化物（4NQO）或该化合物的弱活性3-甲基衍生物中。然后监测这些细胞中的细胞生长抑制、DNA损伤和DNA修复情况。数据表明，4NQO的甲基化修饰实际上改变了这种致癌物诱导的DNA损伤的类型和数量。更具体地说，4NQO在3位的甲基化阻止了4NQO诱导的DNA加合物的形成，这些加合物表现为碱性稳定损伤，其修复在正常细胞中可被阿糖胞苷抑制，但在切除缺陷型XP细胞中存在缺陷。4NQO诱导的碱性不稳定损伤在上述XP细胞中是可修复的，3-甲基衍生物仍可诱导这种损伤，但在等摩尔基础上频率较低。
