Green M H, Waugh A P, Lowe J E, Harcourt S A, Cole J, Arlett C F
MRC Cell Mutation Unit, Sussex University, Falmer, Brighton, UK.
Mutat Res. 1994 Jul;315(1):25-32. doi: 10.1016/0921-8777(94)90024-8.
We have previously shown that non-cycling (unstimulated) human lymphocytes from normal donors show extreme hypersensitivity to UV-B irradiation, and are killed by an excisable lesion which is not a pyrimidine dimer or 6-4 photoproduct. In this paper we show that addition of the 4 deoxyribonucleosides to the medium, each at 10(-5) M, substantially increased the survival of non-cycling normal human T-lymphocytes following UV-B irradiation and substantially reduced the frequency of excision-related strand breaks in human mononuclear cells. Addition of ribonucleosides to the medium did not enhance excision-break rejoining. The survival of fibroblasts, of cycling T-lymphocytes and of unstimulated xeroderma pigmentosum T-lymphocytes was not enhanced by deoxyribonucleosides. This suggests that the hypersensitivity is due to reduced rejoining of excision breaks as a consequence of low intracellular deoxyribonucleotide pools and that it can be redressed by supplementation of the medium with deoxyribonucleosides or upregulation of ribonucleotide reductase following mitogen stimulation. We suggest that UV-B forms an additional DNA lesion which is not a pyrimidine dimer or 6-4 photoproduct, which is relatively common, and at which incision is particularly efficient. In fibroblasts, repair of this lesion is completed with high efficiency, whereas in normal unstimulated T-lymphocytes, rapid incision exacerbates the effects of the reduced rate of strand rejoining and leads to cell death.
我们之前已经表明，来自正常供体的非循环（未受刺激）人类淋巴细胞对UV-B辐射表现出极高的敏感性，并被一种可切除的损伤所杀死，这种损伤不是嘧啶二聚体或6-4光产物。在本文中我们表明，向培养基中添加每种浓度为10^(-5) M的4种脱氧核糖核苷，可显著提高非循环正常人类T淋巴细胞在UV-B照射后的存活率，并显著降低人类单核细胞中与切除相关的链断裂频率。向培养基中添加核糖核苷并不能增强切除-断裂重连。脱氧核糖核苷并未提高成纤维细胞、循环T淋巴细胞和未受刺激的着色性干皮病T淋巴细胞的存活率。这表明，这种高敏感性是由于细胞内脱氧核苷酸池水平低导致切除断裂的重连减少所致，并且可以通过向培养基中补充脱氧核糖核苷或在有丝分裂原刺激后上调核糖核苷酸还原酶来纠正。我们认为，UV-B形成了一种额外的DNA损伤，它不是嘧啶二聚体或6-4光产物，这种损伤相对常见，并且在该损伤处切口特别有效。在成纤维细胞中，这种损伤的修复高效完成，而在正常未受刺激的T淋巴细胞中，快速切口会加剧链重连速率降低的影响并导致细胞死亡。
