Kotova Natalia, Hemminki Kari, Segerbäck Dan
Department of Biosciences, Karolinska Institute, Novum, S-141 57 Huddinge, Sweden.
Cancer Epidemiol Biomarkers Prev. 2005 Dec;14(12):2868-72. doi: 10.1158/1055-9965.EPI-05-0164.
High levels of DNA damage are induced in human skin following exposure to UV radiation. Cyclobutane thymidine dimer (T = T) is the most common of these lesions, which are enzymatically removed as oligonucleotides from DNA and further degraded before excretion in urine. Analysis of such repair products in the urine could serve as a biomarker of total body burden of UV exposure. The aim of this study was to examine the kinetics of T = T excretion following a single tanning session in a commercial solarium and to validate the method by delivering different doses. Ten individuals used the solarium for a total of 35 sessions of body tanning. Urine was collected before UV exposure and daily thereafter (up to 5 or 11 days) and T = T was analyzed using a very sensitive and quantitative (32)P-postlabeling technique combined with high-performance liquid chromatography. Following exposure, T = T levels increased dramatically and reached a peak 3 days later; afterwards, the T = T levels gradually decreased. The total amount of T = T excreted differed about 5-fold among subjects given an equal dose. A 50% excretion time was calculated using the excretion data for the first 5 days and it was found to be between 55 and 76 hours for different individuals. There was a good correlation between the amount of T = T excreted during days 1 to 5 and the delivered UV dose. Reducing exposure time to 50% lowered the amount of T = T to 47%; if half of the lamps were covered, T = T decreased to 44%. Our data show that urinary T = T could be a suitable noninvasive biomarker for UV exposure; a finding which could also be applicable to studies in children.
人体皮肤暴露于紫外线辐射后会诱导产生高水平的DNA损伤。环丁烷胸腺嘧啶二聚体（T=T）是这些损伤中最常见的，这些损伤会作为寡核苷酸从DNA中被酶促去除，并在尿液排泄前进一步降解。分析尿液中的此类修复产物可作为全身紫外线暴露负担的生物标志物。本研究的目的是检查在商业日光浴室进行单次晒黑疗程后T=T排泄的动力学，并通过给予不同剂量来验证该方法。10名个体总共使用日光浴室进行了35次全身晒黑疗程。在紫外线暴露前及之后每天（最多5天或11天）收集尿液，并使用非常灵敏且定量的32P后标记技术结合高效液相色谱法分析T=T。暴露后，T=T水平急剧上升，并在3天后达到峰值；之后，T=T水平逐渐下降。给予相同剂量的受试者中，T=T的排泄总量相差约5倍。使用前5天的排泄数据计算出50%排泄时间，发现不同个体的该时间在55至76小时之间。第1至5天排泄的T=T量与给予的紫外线剂量之间存在良好的相关性。将暴露时间减少至50%会使T=T量降至47%；如果一半灯管被覆盖，T=T量会降至44%。我们的数据表明，尿T=T可能是一种适用于紫外线暴露的非侵入性生物标志物；这一发现也可能适用于儿童研究。
