Reduced levels of UV-induced unscheduled DNA synthesis in epidermal keratinocytes of patients with xeroderma pigmentosum and correlation with development of skin neoplasms.
Primary epidermal keratinocytes obtained from 25 patients with xeroderma pigmentosum (XP) (nine with XP-A, one with XP-C, two with XP-D, five with XP-E, and eight with XP-variant) exhibited less UV-induced unscheduled DNA synthesis (UDS) than did those from 34 normal subjects. Levels of UDS depended greatly on the type of XP; i.e., 3-17% of the control in XP-A, 14% in XP-C, 33-53% in XP-D, 38-77% in XP-E and 58-98% in XP-variant. The extent of UDS in epidermal keratinocytes was almost the same as that in dermal fibroblasts in XP-C, D, and E, but in three out of eight of the XP-variant the level of UDS in epidermal keratinocytes was significantly lower than that in normal subjects. Clinically, three out of nine XP-A patients developed skin neoplasms before 20 years of age. Both patients with XP-D developed skin neoplasms around 40 years of age. In the five XP-E patients, two developed multiple basal cell epithelioma on sun-exposed areas during the forth decade, and one of them also developed squamous cell carcinoma at the age of 50. Four out of the eight patients with the XP-variant developed various skin neoplasms during their 20s and 30s. These results suggest that a defect in UV-induced UDS in epidermal keratinocytes of XP patients is responsible for skin carcinogenesis and the extent to which this defect occurs tends to relate to the age of onset of skin neoplasms.
Kondo
S
S
Department of Dermatology, School of Medicine, Tokyo Medical and Dental University, Japan.
Satoh
Y
Y
Kuroki
T
T
D000328:Adult; D000367:Age Factors; D002648:Child; D004247:DNA / Q000096:biosynthesis / Q000528:radiation effects; D004260:DNA Repair; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D006801:Humans; D007633:Keratins; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000209:etiology*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000150:complications / Q000378:metabolism*
D007633:Keratins; D004247:DNA