Ultraviolet-B-induced apoptosis and cytokine release in xeroderma pigmentosum keratinocytes.
We have assessed the ability of xeroderma pigmentosum and normal keratinocytes grown out from skin biopsies to undergo apoptosis after irradiation with ultraviolet B. Keratinocytes have been studied from xeroderma pigmentosum complementation groups A (three biopsies), C (three biopsies), D (one biopsy), xeroderma pigmentosum variant (two biopsies), and Cockayne syndrome (one biopsy). The three xeroderma pigmentosum group A and the xeroderma pigmentosum group D samples were at least six times more sensitive than normal cells to ultraviolet B-induced apoptosis. The xeroderma pigmentosum variant samples showed intermediate susceptibility. Xeroderma pigmentosum group C samples proved heterogeneous: one showed high sensitivity to apoptosis, whereas two showed near normal susceptibility. The Cockayne syndrome sample showed the high susceptibility of xeroderma pigmentosum groups A and D only at a higher fluence. These results suggest that the relationships between repair deficiency, apoptosis, and susceptibility to skin cancer are not straightforward. Ultraviolet B-induced skin cancer is also thought to be due in part to ultraviolet B-induced impairment of immune responses. The release of the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha from cultured xeroderma pigmentosum keratinocytes tended to occur at lower fluences than in normals, but was less extensive, and was more readily inhibited at higher fluences of ultraviolet B.
Petit-Frère
C
C
MRC Cell Mutation Unit, University of Sussex, Falmer, Brighton, UK.
Capulas
E
E
Lowe
J E
JE
Koulu
L
L
Marttila
R J
RJ
Jaspers
N G
NG
Clingen
P H
PH
Green
M H
MH
Arlett
C F
CF
D017209:Apoptosis / Q000528:radiation effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000528:radiation effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000528:radiation effects; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000473:pathology*
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha