Department of Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, USA.
Photochem Photobiol. 2009 Nov-Dec;85(6):1384-90. doi: 10.1111/j.1751-1097.2009.00591.x.
Exposure to sunlight is responsible for most cutaneous malignant melanomas in the human population. It is very likely that DNA damage is an initial event in melanomagenesis, however, the role played by this damage is an open question. To this end, we used a hemipigmented F(1) hybrid of the fish genus Xiphophorus and HPLC tandem mass spectrometry to examine the effects of melanin on the induction and repair of the predominant UV-induced photoproducts formed in skin cell DNA. We found that heavily pigmented skin cells had about half the damage of nonpigmented cells and the relative induction of the major photoproducts was independent of the degree of pigmentation. The efficiency of photoenzymatic repair was the same in nonpigmented and pigmented areas of the fish. We found no evidence of residual damage at 10 days after the last exposure. Most striking was that repeated exposure to multiple doses of UVB caused a very significant photoadaptive response. Rather than an accumulation of damage after five doses of UVB we saw a significant reduction in the amount of damage induced after the final dose compared with the initial dose. The relevance of these observations is discussed in the context of melanoma susceptibility and UVB thresholds.
阳光照射是导致人类大多数皮肤恶性黑色素瘤的原因。很可能 DNA 损伤是黑色素瘤发生的初始事件，然而，这种损伤所起的作用仍是一个悬而未决的问题。为此，我们使用了鱼类剑尾鱼的半色素化 F(1)杂种，以及 HPLC 串联质谱，来研究黑色素对皮肤细胞 DNA 中形成的主要 UV 诱导光产物的诱导和修复的影响。我们发现，色素沉着严重的皮肤细胞的损伤程度只有非色素沉着细胞的一半，而主要光产物的相对诱导与色素沉着程度无关。鱼的非色素沉着和色素沉着区域的光酶修复效率相同。在最后一次暴露 10 天后，我们没有发现残留损伤的证据。最引人注目的是，多次重复暴露于 UVB 会引起非常显著的光适应性反应。与在五次 UVB 剂量后积累损伤不同，我们发现与初始剂量相比，最后一次剂量诱导的损伤量显著减少。这些观察结果的相关性在黑色素瘤易感性和 UVB 阈值的背景下进行了讨论。
