Department of Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX, USA.
Photochem Photobiol. 2011 Mar-Apr;87(2):335-41. doi: 10.1111/j.1751-1097.2010.00875.x. Epub 2011 Jan 11.
Nucleotide excision repair (NER) is the primary defense against the DNA damage implicit in skin cancer formation and is negatively affected by chronic exposure to UVB radiation. However, in situ and in vitro studies consistently yield equivocal results when addressing individual DNA repair capacity and melanoma susceptibility. The primary objective of this study was to determine if individual global NER capacity is a risk factor for melanoma formation in a prominent UVB-inducible melanoma model, hybrid Xiphophorus fishes. After neonatal UVB irradiation, adult tumor-bearing and tumor-free fish were given a challenge UVB dose and (6-4) photoproduct repair was quantified in individual fish at 24 h using radioimmunoassay. Despite considerable inter-individual variation in repair capacity, ranging from 13% to 91%, we found no difference in mean NER capacity between fish with and without melanomas, thus detaching global NER from melanomagenesis. Furthermore, despite epidemiological data indicating that sex and age are important risk factors underlying melanoma susceptibility, we found no difference in mean NER rates among the sexes or as a function of age. We conclude with a discussion of the apparent paradox of how inter-individual variation in NER is not a risk factor given the clear evidence that DNA damage underlies melanoma susceptibility.
核苷酸切除修复 (NER) 是防御皮肤癌形成中所隐含的 DNA 损伤的主要机制，而慢性暴露于 UVB 辐射会对其产生负面影响。然而，在研究个体 DNA 修复能力与黑色素瘤易感性时，体内和体外研究的结果始终存在分歧。本研究的主要目的是确定个体整体 NER 能力是否是在一个突出的 UVB 诱导性黑色素瘤模型（杂交剑尾鱼）中形成黑色素瘤的危险因素。在新生儿接受 UVB 照射后，成年带瘤和无瘤鱼接受挑战剂量的 UVB 照射，并在 24 小时内使用放射免疫测定法在个体鱼中定量（6-4）光产物修复。尽管修复能力存在相当大的个体间差异，范围从 13%到 91%，但我们发现有黑色素瘤和无黑色素瘤的鱼之间的平均 NER 能力没有差异，从而将整体 NER 与黑色素瘤发生分离。此外，尽管流行病学数据表明性别和年龄是黑色素瘤易感性的重要危险因素，但我们没有发现性别的平均 NER 率或年龄与 NER 率之间存在差异。最后，我们讨论了一个明显的悖论，即个体间 NER 的差异如何不是一个危险因素，而 DNA 损伤是黑色素瘤易感性的基础。
