Hypersensitivity of human lymphocytes to UV-B and solar irradiation.
T-lymphocytes from three normal human donors, irradiated with broad-spectrum UV-B (peak emission, 312 nm), are 20-fold more sensitive than fibroblasts from four normal donors in a clonogenic assay. We have compared the formation of thymine cyclobutane dimers and pyrimidine-(6-4)-pyrimidone photoproducts following irradiation by UV-C (254 nm) and UV-B and studied killing at doses giving equal dimer formation. UV-B killing of fibroblasts appears to be associated with dipyrimidine photoproduct formation, whereas UV-B killing of lymphocytes is mediated by nondimer damage. Strand breakage following UV-B irradiation measured using the "Comet" assay (single cell gel electrophoresis) reflects this nondimer damage and has kinetics consistent with excisable damage. Lymphocytes from three excision-deficient xeroderma pigmentosum donors show reduced strand breakage and increased killing following UV-B irradiation, compared with lymphocytes from normal donors. We therefore suggest that UV-B kills human lymphocytes by excisable nondimer damage and that xeroderma pigmentosum lymphocytes are defective in its repair. The putative nondimer damage does not appear to be associated with radical attack, and the strand breakage is not a manifestation of apoptosis. A 1-min exposure of human lymphocytes in vitro to natural sunlight is sufficient to produce damage measurable by the Comet assay.
Arlett
C F
CF
MRC Cell Mutation Unit, Sussex University, Falmer, Brighton, England.
Lowe
J E
JE
Harcourt
S A
SA
Waugh
A P
AP
Cole
J
J
Roza
L
L
Diffey
B L
BL
Mori
T
T
Nikaido
O
O
Green
M H
MH
D017209:Apoptosis / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D005347:Fibroblasts / Q000528:radiation effects; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000528:radiation effects; D012680:Sensitivity and Specificity; D013472:Sunlight / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000528:radiation effects*; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects*
D005609:Free Radicals; D004247:DNA