DNA repair responses in human skin cells.
DNA repair responses in human skin cells.
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人类皮肤细胞中的 DNA 修复反应。
DOI：
10.1111/1523-1747.ep12479265
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Parsons,CS
中科院分区：
文献类型：
--
作者：
Hanawalt,PC;Liu,SC;Parsons,CS
阳光和一些环境化学物质会在人体皮肤细胞的DNA中产生损伤，如果不加以修复，可能会干扰这些细胞的正常功能。这种相互作用最严重的结果可能是恶性肿瘤。因此，重要的是要发展机制的理解，通过这些机制，病变可以修复或耐受而不会产生有害的后果。我们对受损DNA分子处理的模型很大程度上来源于对细菌系统的研究。当对这些模型进行人体细胞反应测试时，发现了一些相似之处，但也有显著的差异。了解表皮角质形成细胞的DNA修复反应也很重要，以便与真皮成纤维细胞进行的更广泛的研究进行比较。到目前为止，我们的实验结果表明紫外线诱导的嘧啶二聚体在人角质形成细胞和成纤维细胞中的切除-修复具有相似性。光激活的8-甲氧基补骨脂素（PUVA）在DNA中产生的单加合物和链间交联都可以在正常的人成纤维细胞中修复，而在色素干燥病患者中则不能。单加合物，如嘧啶二聚体，可能是更致突变/致癌的病变，而交联更不容易修复，可能导致更有效的DNA功能阻断。这表明，在银屑病的PUVA治疗中，最大限度地产生交联，同时最大限度地减少单加合物的产生的分剂量方案可能比单次紫外线照射方案更有效，潜在的致癌性更低。
Sunlight and some environmental chemical agents produce lesions in the DNA of human skin cells that if unrepaired may interfere with normal functioning of these cells. The most serious outcome of such interactions may be malignancy. It is therefore important to develop an understanding of mechanisms by which the lesions may be repaired or tolerated without deleterious consequences. Our models for the molecular processing of damaged DNA have been derived largely from the study of bacterial systems. Some similarities but significant differences are revealed when human cell responses are tested against these models. It is also of importance to learn DNA repair responses of epidermal keratinocytes for comparison with the more extensive studies that have been carried out with dermal fibroblasts. Our experimental results thus far indicate similarities for the excision-repair of ultraviolet-induced pyrimidine dimers in human keratinocytes and fibroblasts. Both the monoadducts and the interstrand crosslinks produced in DNA by photoactivated 8-methoxypsoralen (PUVA) can be repaired in normal human fibroblasts but not in those from xerodenna pigmentosum patients. The monoadducts, like pyrimidine dimers, are probably the more mutagenic/carcinogenic lesions while the crosslinks are less easily repaired and probably result in more effective blocking of DNA function. It is suggested that a split-dose protocol that maximizes the production of cross-links while minimizing the yield of monoadducts may be more effective and potentially less carcinogenic than the single ultraviolet exposure regimen in PUVA therapy for psoriasis.