Berg R J, de Vries A, van Steeg H, de Gruijl F R
Department of Dermatology, University Hospital Utrecht, the Netherlands.
Cancer Res. 1997 Feb 15;57(4):581-4.
Although xeroderma pigmentosum (XP) patients are rare, carriers of XP genes (heterozygotes) are much more common. Whether such carriers have an increased skin cancer risk is unknown. Recently developed mouse models for XP have opened up the possibility of determining the skin cancer risk of heterozygotes relative to wild types. Therefore, the XPA knockout trait has been crossed into hairless mice, and squamous cell carcinomas of the skin have been induced by low daily UVB exposures for 500 days in all three genotypes (-/-, +/-, and +/+). The carcinogenic response of the heterozygotes did not significantly differ from that of their wild-type littermates. Tumors in the XPA -/- animals appeared with a latency time that was decreased by a factor of 4.2. From this, we estimate that a functional XPA gene provides a "protection factor" of 60 (95% confidence interval, 15-250) against UV carcinogenesis, which is greater protection than that against acute UV effects, such as erythema and edema (protection factor between 7 and 16). Deficient nucleotide excision repair appears to have a more dramatic impact on skin cancer susceptibility than on sensitivity to acute UV effects.
尽管着色性干皮病（XP）患者很罕见，但XP基因携带者（杂合子）却更为常见。此类携带者患皮肤癌的风险是否增加尚不清楚。最近开发的XP小鼠模型为确定杂合子相对于野生型的皮肤癌风险提供了可能。因此，已将XPA基因敲除性状导入无毛小鼠，并对所有三种基因型（-/-、+/-和+/+）的小鼠进行了为期500天的低剂量每日紫外线B照射，以诱发皮肤鳞状细胞癌。杂合子的致癌反应与其野生型同窝小鼠没有显著差异。XPA -/-动物的肿瘤出现的潜伏期缩短了4.2倍。据此，我们估计一个功能性XPA基因对紫外线致癌作用提供了60（95%置信区间，15 - 250）的“保护因子”，这比其对急性紫外线效应（如红斑和水肿）的保护作用（保护因子在7至16之间）更大。核苷酸切除修复缺陷似乎对皮肤癌易感性的影响比对急性紫外线效应敏感性的影响更为显著。
