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 lymphoc ytes from normal donors show extreme hypersensitivity to UV-B irradiat ion, and are killed by an excisable lesion which is not a pyrimidine d imer or 6-4 photoproduct. In this paper we show that addition of the 4 deoxyribonucleosides to the medium, each at 10(-5) M, substantially i ncreased the survival of non-cycling normal human T-lymphocytes follow ing UV-B irradiation and substantially reduced the frequency of excisi on-related strand breaks in human mononuclear cells. Addition of ribon ucleosides 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 deoxyribonucl eosides. This suggests that the hypersensitivity is due to reduced rej oining of excision breaks as a consequence of low intracellular deoxyr ibonucleotide pools and that it can be redressed by supplementation of the medium with deoxyribonucleosides or upregulation of ribonucleotid e reductase following mitogen stimulation. We suggest that UV-B forms an additional DNA lesion which is not a pyrimidine dimer or 6-4 photop roduct, which is relatively common, and at which incision is particula rly 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 rejoini ng and leads to cell death.