Ultraviolet-B-induced apoptosis and cytokine release in xeroderma pigmentosum keratinocytes

We have assessed the ability of xeroderma pigmentosum and normal keratinocy tes grown out from skin biopsies to undergo apoptosis after irradiation wit h ultraviolet B. Keratinocytes have been studied from xeroderma pigmentosum complementation groups A (three biopsies), C (three biopsies), D (one biop sy), xeroderma pigmentosum variant (two biopsies), and Cockayne syndrome (o ne biopsy). The three xeroderma pigmentosum group A and the xeroderma pigme ntosum group D samples were at least six times more sensitive than normal c ells to ultraviolet B-induced apoptosis. The xeroderma pigmentosum variant samples showed intermediate susceptibility. Xeroderma pigmentosum group C s amples proved heterogeneous: one showed high sensitivity to apoptosis, wher eas two showed near normal susceptibility. The Cockayne syndrome sample sho wed the high susceptibility of xeroderma pigmentosum groups A and D only at a higher fluence. These results suggest that the relationships between rep air deficiency, apoptosis, and susceptibility to skin cancer are not straig htforward. Ultraviolet B-induced skin cancer is also thought to be due in p art to ultraviolet B-induced impairment of immune responses. The release of the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha f rom cultured xeroderma pigmentosum keratinocytes tended to occur at lower f luences than in normals, but was less extensive, and was more readily inhib ited at higher fluences of ultraviolet B.