Photoadaptation to ultraviolet (UV) radiation in vivo: photoproducts in epidermal cells following UVB therapy for psoriasis

Background Ultraviolet (UV) radiation is mutagenic and induces specific DNA lesions in human skin that are often found at dipyrimidine sites. These ph otoproducts are likely to be biologically relevant regarding skin carcinoge nesis, as p53 mutations in skin tumours are most often found at these UV ra diation-specific sites within DNA. Psoriasis patients receiving long-term p hototherapy are at an increased risk of non-melanoma skin cancers. Objectives The aim of this study was to quantify DNA photoproducts in human epidermis in vivo following consecutive doses of UVB and to investigate va riations in DNA damage according to skin type. UVB dose and age. Methods Eleven psoriasis patients receiving UVB phototherapy three times a week were recruited and underwent skin biopsies on a non-sun-exposed site b efore starting phototherapy and after three, nine and 18 UVB exposures. A b iopsy was also taken at least 4 weeks after stopping phototherapy. DNA was extracted from separated epidermis and three types of photoproducts were qu antified using a novel P-32 high-performance liquid chromatographic techniq ue. Results The mean level of cyclobutane dipyrimidine dimers (CPDs) after thre e doses of UVB (dose range 0 . 03-0 . 15 J cm(-2)) was 3 . 2 (range 0 . 8-8 . 9) photoproducts per 10(6) normal nucleotides for TT=T dimers and 4 . 5 (range 0-14) per 106 normal nucleotides for TT=C dimers. The mean levels of TT-C 6-4 photoproducts after three doses of UVB were very low (0 . 2, rang e 0-1 . 8). Overall, the levels of TT=T and TT=C reached a plateau at three exposures and were found to decrease for subsequent exposures despite incr easing UVB doses. Skin type was negatively associated with mean levels of C PDs. However, significant differences in levels of photoproducts were seen between individuals, even after adjusting for skin type. No association was found between challenge dose of UVB and photoproduct yield in this study. Conclusions This study showed a great individual variation in the accumulat ion of DNA photoproducts following exposure to repetitive doses of UVB, Pho toadaptive responses of human skin involving DNA repair, tanning and epider mal thickening are likely to explain the overall lack of increase in DNA le sions throughout phototherapy. This in vivo study confirms that psoriasis p atients produce a significant amount of DNA photolesions at suberythemal do ses of UVB. Further work is needed to investigate which host factors are mo st likely to predict susceptibility to UV radiation-induced DNA damage.