Effect of deoxyribonucleosides on the hypersensitivity of human peripheral blood lymphocytes to UV-B and UV-C irradiation.
We have previously shown that non-cycling (unstimulated) human lymphocytes from normal donors show extreme hypersensitivity to UV-B irradiation, and are killed by an excisable lesion which is not a pyrimidine dimer or 6-4 photoproduct. In this paper we show that addition of the 4 deoxyribonucleosides to the medium, each at 10(-5) M, substantially increased the survival of non-cycling normal human T-lymphocytes following UV-B irradiation and substantially reduced the frequency of excision-related strand breaks in human mononuclear cells. Addition of ribonucleosides to the medium did not enhance excision-break rejoining. The survival of fibroblasts, of cycling T-lymphocytes and of unstimulated xeroderma pigmentosum T-lymphocytes was not enhanced by deoxyribonucleosides. This suggests that the hypersensitivity is due to reduced rejoining of excision breaks as a consequence of low intracellular deoxyribonucleotide pools and that it can be redressed by supplementation of the medium with deoxyribonucleosides or upregulation of ribonucleotide reductase following mitogen stimulation. We suggest that UV-B forms an additional DNA lesion which is not a pyrimidine dimer or 6-4 photoproduct, which is relatively common, and at which incision is particularly efficient. In fibroblasts, repair of this lesion is completed with high efficiency, whereas in normal unstimulated T-lymphocytes, rapid incision exacerbates the effects of the reduced rate of strand rejoining and leads to cell death.
Green
M H
MH
MRC Cell Mutation Unit, Sussex University, Falmer, Brighton, UK.
Waugh
A P
AP
Lowe
J E
JE
Harcourt
S A
SA
Cole
J
J
Arlett
C F
CF
D002478:Cells, Cultured; D003853:Deoxyribonucleosides / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000528:radiation effects; D006801:Humans; D008213:Lymphocyte Activation; D008934:Mitogens; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000528:radiation effects*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000473:pathology
D003853:Deoxyribonucleosides; D008934:Mitogens; D011837:Radiation-Protective Agents