Clinical and photobiological characteristics of Japanese xeroderma pigmentosum variant

Clinical and photobiological differences between Japanese patients belonging to xeroderma pigmentosum (XP) variant and complementation group A were studied, especially focussing on XP variants. All of the XP variant patients commonly manifested a delayed onset of pigmented freckles as the initial symptom around 5--7 years old without acute sun erythema, in contrast to the early manifestation of acute solar erythema during infancy in XP group A patients. Six XP variant patients tested showed normal and three showed low minimal erythema doses (MEDs), at the 24 h reaction peak after monochromatic u.v. (280--330 nm) irradiation, while XP group A patients had definitely low MEDs (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 u.v.-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 u.v. cell killing than did normal cells. With respect to the synergistic effect of caffeine on u.v. lethality, XP variant strains could be divided into caffeine-susceptible (eight cases) and caffeine-resistant (two cases) subgroups. The extent of excision-break accumulation was greater in the former subgroup than in the latter. All of eight XP variant patients whose cells showed caffeine potentiation of u.v. lethality had already had skin malignancies, but two sib patients whose cells were caffeine-resistant had as yet had no neoplasm. It is strongly suggested that in XP variant, caffeine-susceptibility may be related to the development of neoplasms.