In situ repair of cyclobutane pyrimidine dimers in skin and melanocytic nevi of cutaneous melanoma patients.
The development of cutaneous malignant melanoma (CMM) and its precursor lesions, melanocytic nevi, has been linked to sun exposure. Cyclobutane pyrimidine dimers (CPDs) are the majority of DNA lesions induced by sun exposure. In our study, we investigated if CMM patients have impaired ability to repair CPDs in skin as well as in melanocytic nevi. The repair kinetics were followed up to 3 weeks after exposure to 40 mJ/cm(2) of solar simulating radiation. Altogether 12 CMM patients and 10 healthy controls were included in our study. Buttock skin biopsies were taken at 0 hr, 48 hr and 3 weeks after UV exposure, whereas melanocytic nevi and surrounding skin biopsies were taken only at 0 hr and 3 weeks. The CPD levels were measured by a (32)P-postlabeling method. The results showed that the repair rate of CPDs in neither the skin nor the nevi was significantly different between the CMM patients and the control group. For both groups, the repair rate of TT = C was faster than that for TT = T. The important finding is that about 10% of the initial TT = T damage remained unrepaired after 3 weeks, and was detectable in normal epidermis as well as in nevi of all subjects. We also found that the amount of TT = C and TT = T at 0 hr in nevi was significantly lower than that in surrounding skin (Wilcoxon rank sum test, p < 0.05).
Zhao
Chunyan
C
Department of Biosciences at Novum, Karolinska Institute, Huddinge, Sweden. chunyan.zhao@cnt.ki.se
Snellman
Erna
E
Jansen
Christer T
CT
Hemminki
Kari
K
D000328:Adult; D001706:Biopsy; D002851:Chromatography, High Pressure Liquid; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000378:metabolism*; D011740:Pyrimidine Dimers / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014466:Ultraviolet Rays
D004273:DNA, Neoplasm; D011740:Pyrimidine Dimers