| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
Cleaver et al. have established UV-resistant xeroderma pigmentosum (XP) revertant cells from UV-sensitive XP-A cells by chemical treatment. Surprisingly, UV-resistant XP revertant cells are still deficient in the repair of cyclobutane pyrimidine dimers, although they have recovered the repair ability of (6-4) photoproducts, suggesting that (6-4) photoproducts are the main UV-induced lethal lesions. To confirm these results, I examined UV-induced cytotoxicity in XP-A, XP revertant and normal human cells by colony formation method. XP-A cells were 10 times as UVsensitive as normal cells. I found that XP revertant cells had obtained almost normal UV sensitivity as reported by Cleaver et al. Next, the repair of two types of DNA damage (cyclobutane dimers and (6-4) photoproducts) was examined by the sensitive ELISA using monoclonal antibodies, which I had newly established, against photolesions. In the repair of (6-4) photoproducts, XP-A repaired only 30% within 24 hr after irradiation (10 J/m^2), while normal cells repaired more than 90% within 3 hr. XP revertant showed almost normal repair pattern. In the repair of cyclobutane dimers, XP-A, XP revertant and normal cells repaired 20%, 40% and 60% within 24 hr after irradiation, respectively. I confirmed Cleaver's results showing that XP-revertant had almost normal repair on (6-4) photoproducts, but had reduced repair on cyclobutane dimers. However, I found that XP revertant did have reduced repair on cyclobutane dimers, but not completely inhibited repair reported by Cleaver et al. The results were confirmed by the repair experiment using low UV dose (2 J/m^2). These results suggest that XP revertant cells still have some residual repair capacity for cyclobutane dimers. Thus, these results suggest that cyclobutane pyrimidine dimers are not excluded as a candidate for the main UV-induced lethal damage.
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