van Kranen H J, de Laat A, van de Ven J, Wester P W, de Vries A, Berg R J, van Kreijl C F, de Gruijl F R
Laboratory of Health Effects Research, National Institute of Public Health and the Environment, BA Bilthoven, the Netherlands.
Cancer Res. 1997 Apr 1;57(7):1238-40.
Mutations with clear "UVB fingerprints" have been observed in the p53 gene of human nonmelanoma skin tumors and of experimentally UVB-induced murine skin tumors. Although UVA (315-400 nm) radiation is also a complete carcinogen, its contribution to sunlight-induced mutagenesis remains poorly characterized. There is experimental evidence that the production of reactive oxygen species plays a more dominant role with long-wave UVA than with UVB radiation. We have induced skin tumors (n = 42) in hairless SKH:HR1 mice (n = 14) by daily exposure to long-wave UVA (365-nm) radiation. The incidence of p53 alterations in these tumors is low compared to UVB-induced tumors; positive staining for the p53 protein was observed in only 50% of the tumors, and less than 15% of the tumors showed a mutation in one of the exons 5, 7, or 8 of the p53 gene. The pattern of p53 staining was more irregular and less dense compared to UVB, and the mutations (all C-->T) were mainly (six of seven) located at codon 267. Besides a general p53 hotspot, this codon is also the main hotspot for UVB-induced skin tumors in these mice. No mutations specific for UVA, ie., mutations specific for reactive oxygen species, could be detected.
在人类非黑色素瘤皮肤肿瘤以及实验性紫外线B（UVB）诱导的小鼠皮肤肿瘤的p53基因中，已观察到具有清晰“UVB指纹”的突变。尽管紫外线A（UVA，315 - 400纳米）辐射也是一种完全致癌物，但其对阳光诱导的诱变作用仍未得到充分表征。有实验证据表明，活性氧的产生在长波UVA辐射中比在UVB辐射中发挥更主导的作用。我们通过每天暴露于长波UVA（365纳米）辐射，在无毛SKH:HR1小鼠（n = 14）中诱导出了皮肤肿瘤（n = 42）。与UVB诱导的肿瘤相比，这些肿瘤中p53改变的发生率较低；仅在50%的肿瘤中观察到p53蛋白阳性染色，并且不到15%的肿瘤在p53基因的外显子5、7或8之一中显示出突变。与UVB相比，p53染色模式更不规则且密度更低，并且突变（全部为C→T）主要（七例中的六例）位于密码子267处。除了一个普遍的p53热点外，该密码子也是这些小鼠中UVB诱导的皮肤肿瘤的主要热点。未检测到UVA特异性的突变，即活性氧特异性的突变。
