The induction and repair of DNA damage and its influence on cell death in primary human fibroblasts exposed to UV-A or UV-C irradiation.

Irradiation with UV-A of normal human fibroblasts in phosphate-buffered saline induced cell death, measured as lack of colony-forming ability. A specially filtered sunlamp, emitting wavelengths greater than 330 nm, was used as UV-A source. After UV-A irradiation, single-strand breaks (alkali-labile bonds) could be detected in DNA; these lesions were rapidly repaired. The induction of these single-strand breaks was almost eliminated when irradiation was performed in the presence of catalase. However, catalase, when present during UV-A irradiation, did not reduce cell death of the fibroblasts. Excision repair, monitored as unscheduled DNA synthesis, was induced strongly by irradiation with UV-C (predominantly 254 nm), but could not be detected after UV-A irradiation. Moreover, very little accumulation of incision breaks during post-irradiation incubation with hydroxyurea and 1-beta-D-arabinofuranosylcytosine (araC) was detected after UV-A. This is consistent with the low amount of pyrimidine dimers (measured as UV-endonuclease susceptible sites) induced by UV-A. Xeroderma pigmentosum fibroblasts of complementation group A, which are extremely sensitive to UV-C irradiation, showed the same sensitivity to UV-A as normal fibroblasts. The results indicate that lethality by UV-A wavelengths greater than 330 nm is caused by lesions other than single-strand breaks (alkali-labile bonds) and pyrimidine dimers.