Parshad R, Gantt R, Sanford K K, Jones G M, Camalier R F
Int J Cancer. 1981 Sep 15;28(3):335-40. doi: 10.1002/ijc.2910280313.
Skin fibroblasts from ataxia telangiectasia and xeroderma pigmentosum (XP) donors and from the XP sib (possible heterozygote), all genetically predisposed to a high risk of cancer, show an increased susceptibility to light-induced chromatid breaks after culture in vitro. Light-induced chromatid breaks were shown previously to result from generation of hydrogen peroxide (H2O2) during light exposure. The level of susceptibility attained is significantly higher than that observed in 13 lines of fibroblasts from normal skin of donors ranging in age from 3 days to 92 years or from fetal skin tested at various population doubling levels. Two lines of normal skin fibroblasts transformed by chemical carcinogens to neoplastic cells also show a significant increase in susceptibility as compared with their untransformed controls. These data indicate for human cells, as reported earlier for mouse cells, an association between enhanced susceptibility to light-induced chromatid damage and neoplastic potential; this association is further supported by the high susceptibility of cells derived from a human adenocarcinoma. Two observations are consistent with the concept that the increased susceptibility does not result from greater initial damage to the DNA of the neoplastic cells. First, activities of the ubiquitous H2O2 scavenging enzyme, glutathione peroxidase, are similar in the paired normal and neoplastic cell populations. Second, cells of the paired lines are equally sensitive to DNA breakage by exogenous H2O2. The enhanced susceptibility associated with neoplastic potential may result from an impaired capacity to repair DNA rather than a greater initial sensitivity of the neoplastic cells to the damaging agent.
共济失调毛细血管扩张症和着色性干皮病（XP）患者及其XP同胞（可能为杂合子）的皮肤成纤维细胞，均具有遗传易感性，患癌风险高，在体外培养后对光诱导的染色单体断裂表现出更高的敏感性。先前已表明，光诱导的染色单体断裂是由光照期间过氧化氢（H2O2）的生成所致。所达到的敏感性水平显著高于从3天至92岁供体的正常皮肤或在不同群体倍增水平下测试的胎儿皮肤中获取的13株成纤维细胞系所观察到的水平。通过化学致癌物转化为肿瘤细胞的两株正常皮肤成纤维细胞系，与其未转化的对照相比，也显示出敏感性显著增加。这些数据表明，对于人类细胞，如同先前对小鼠细胞的报道，对光诱导的染色单体损伤的易感性增强与肿瘤发生潜能之间存在关联；来自人类腺癌的细胞的高敏感性进一步支持了这一关联。两项观察结果与易感性增加并非源于肿瘤细胞DNA的更大初始损伤这一概念一致。首先，普遍存在的H2O2清除酶谷胱甘肽过氧化物酶的活性在配对的正常和肿瘤细胞群体中相似。其次，配对细胞系的细胞对外源性H2O2引起的DNA断裂同样敏感。与肿瘤发生潜能相关的易感性增强可能是由于DNA修复能力受损，而非肿瘤细胞对损伤剂的初始敏感性更高。
