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The human population is exposed to both the ultraviolet A (UVA) and B (UVB) regions of the solar spectrum. UVB induces mainly dipyrimidine photoproducts in DNA by a direct photochemical mechanism, whereas UVA is absorbed by other cellular constituents and induces mainly oxidative damage indirectly. The proportions of the different dipyrimidine photoproducts, and the ratio of dipyrimidine to oxidative damage depend on the exact spectral output of a UV source. Irradiation of human epidermal keratinocytes induces release of cytokines, with cyclobutane pyrimidine dimers playing a significant role in the process. These cytokines may then modulate the activity of cells of the immune system. Freshly isolated human lymphocytes are exquisitely sensitive to UVB irradiation, because of their low deoxyribonucleotide pools. They also have a separate defect in removal of cyclobutane pyrimidine dimers from their DNA. We have observed that frequencies of mutations at the hprt locus in human T-lymphocytes and translocations involving the bcl2 locus in B-lymphocytes appear to be associated with sunlight levels over the period before the blood sample was taken. This may be an indirect cytokine-mediated effect, and may be relevant to the possible link between non-Hodgkin's lymphoma and sunlight. On the other hand, sunlight can have beneficial effects, and may protect against autoimmune diseases including type I diabetes and multiple sclerosis.

We have selected two N-methyl-N-nitrosourea (MNU)-resistant derivatives of the SV40-transformed, alkyltransferase-deficient (Mex-) human fibroblast cell line MRC5V1. Both derivatives remain Mex-. They are cross-resistant to methylmethanesulphonate (MMS) and 6-thioguanine (6TG) but not 2,6-diaminopurine. They show increased sensitivity to the bifunctional chloroethylating agent mitozolomide (MTZ). We have transfected MRC5V1 and one of our MNU-resistant lines with the bacterial O6-methylguanine (O6-MeG)-DNA methyltransferase (ada) gene. Transfectants of MRC5V1 are significantly more resistant to MNU but exhibit only a small increase in resistance to MMS and MTZ. Transfectants of the MNU-resistant derivative exhibit only a small additional increase in resistance to MNU, no further increase in resistance to MMS and a large increase in resistance to MTZ. The pattern of resistance to cytotoxic agents of these transfectants suggests that a second mechanism of resistance to MNU, independent of alkyltransferase expression, is operating in our resistant lines. This mechanism apparently enables the cells to tolerate O6-MeG and 6TG, but not chloroethyl adducts in their DNA.