Differential behaviors toward ultraviolet A and B radiation of fibroblastsand keratinocytes from normal and DNA-repair-deficient patients

Xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) are rare genoderma toses transmitted as recessive and autosomal traits that result in reduced capacity to repair UV-induced DNA lesions. Although XP, but not TTD, patien ts are Drone to basal and squamous cell carcinomas, to date no comparative studies of the XP and TTD phenotypes have included epidermal keratinocytes. We compared the DNA repair rapacity (by unscheduled DNA synthesis) and cel l survival (by clonal analysis) of epidermal keratinocytes and dermal fibro blasts grown from normal individuals and patients with xeroderma pigmentosu m and trichothiodystrophy following UVA and UVB irradiation. The same dose of UVB (1000 J/m(2)) induced twice as many DNA. lesions in normal fibroblas ts as in normal keratinocytes, UV survival rates were always higher in kera tinocytes than in fibroblasts. Normal and TTD keratinocytes survived better following UVA and UVB irradiation than XP-C and XP-D keratinocytes, XP-C k eratinocytes exhibited exacerbated sensitivity toward UVA radiation. Unsche duled DNA synthesis at UV doses leading to 50% cell survival indicated that the ratio of DNA repair capacity to cell survival Is higher in keratinocyt es than in fibroblasts. In addition, UVA and UVB irradiation induced a tran sition from proliferative to abortive keratinocyte colonies. This transitio n varied between donors and was in part correlated with their cancer suscep tibility. Altogether these data provide the first evidence of the different ial behaviors of normal, XP, and TTD keratinocytes toward UV radiation.