Clinical and photobiological characteristics of Japanese xeroderma pigmentosum variant*

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Abstract
Clinical and photobiological differences between Japanese patients belonging to xeroderma pigmentosum (XP) variant and complementation group A were studied, focusing on XP variants. All of 10 XP variant patients manifested pigmented freckles as the initial symptom around 5-7 yr old without acute sun erythema in contrast to the manifestation of acute solar erythema during infancy in XP group A patients. Six XP variant patients tested showed normal and 3 showed low minimal erythema doses (MED) at the 24 h reaction peak after monochromatic UV (28c-330 nm) irradiation, while XP group A patients had definitely low MED (280-350 nm) with abnormally delayed peaking of the erythema reaction at 72 h. In cell culture studies all XP variant strains exhibited normal levels of 254 nm UV-induced unscheduled DNA synthesis (UDS), 1.4-2 times more accumulation of excision DNA breaks by arabinofuranosyl cytosine and hydroxyurea due to a subtle defect in the later polymerization step of excision repair, and a slightly higher sensitivity to UV cell killing than did normal cells. With respect to the synergistic effect of caffeine on UV lethality, XP variant strains could be divided into caffeine-susceptible (8 cases) and caffeine-resistant (2 cases) subgroups. The extent of excision-break accumulation was greater in the former subgroup than in the latter. All of 8 XP variant patients whose cells showed caffeine potentiation of UV lethality had already had skin malignancies, but 2 sib patients whose cells were caffeine-resistant had as yet had no neoplasm. In XP variant, caffeine-susceptibility may be related to the development of neoplasms.