Photocarcinogenesis and inhibition of intercellular adhesion molecule 1 expression in cells of DNA-repair-defective individuals.
Cells from patients with xeroderma pigmentosum complementation group D (XP-D) and most patients with trichothiodystrophy (TTD) are deficient in excision repair of ultraviolet (UV) radiation-induced DNA damage. Although in both syndromes this defect is based on mutations in the same gene, XPD, only XP-D, not TTD, individuals have an increased risk of skin cancer. Since the reduction in DNA repair capacity is similar in XP-D and TTD patients, it cannot account for the difference in skin cancer risk. The features of XP-D and TTD might therefore be attributable to differences in the immune response following UV-irradiation, a factor which is presumed to be important for photocarcinogenesis. We have measured the capacity of UVB radiation to inhibit expression of the immunological key molecule intercellular adhesion molecule 1 (ICAM-1) in cells from three healthy individuals in comparison to cells from three XP-D and three TTD patients. Cells from XP-D patients, but not from TTD patients, exhibited an increased susceptibility to UVB radiation-induced inhibition of ICAM-1 expression. Transfection of XP-D cells with the wild-type XPD cDNA, but not with XPC cDNA, corrected this abnormal phenotype. Thus, the skin cancer risk in DNA repair-defective individuals correlated with the susceptibility of their cells to UVB radiation-induced inhibition of ICAM-1 expression, rather than with their defect in DNA repair. The XPD protein has dual roles: in DNA repair and transcription. The transcriptional role might be important for the control of expression of immunologically relevant genes and thereby contribute to the skin cancer risk of a DNA-repair-deficient individual.
Ahrens
C
C
Clinical and Experimental Photodermatology, Department of Dermatology, Heinrich Heine University, Moorenstrasse 5, D-40225 Düsseldorf, Germany.
Grewe
M
M
Berneburg
M
M
Grether-Beck
S
S
Quilliet
X
X
Mezzina
M
M
Sarasin
A
A
Lehmann
A R
AR
Arlett
C F
CF
Krutmann
J
J
D002478:Cells, Cultured; D004260:DNA Repair / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D006130:Growth Disorders / Q000235:genetics / Q000473:pathology; D006197:Hair / Q000002:abnormalities*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D012867:Skin / Q000473:pathology* / Q000528:radiation effects; D013577:Syndrome; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000473:pathology
D018799:Intercellular Adhesion Molecule-1