Interaction of human and chick DNA repair functions in UV-irradiated xeroderma pigmentosum-chick erythrocyte heterokaryons.
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Biomedical subjects
Publications and source records attributed to E A De Weerd-Kastelein.
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The role of DNA repair mechanisms in the induction of sister chromatid exchanges (SCE) after exposure to ultraviolet radiation was investigated in xeroderma pigmentosum cells. Cells from different excision-deficient XP strains, representing the 5 complementation groups in XP, A, B, C, D and E, and from excision-proficient XP variant strains were irradiated with low doses of UVR (0-3.5 J/m2). The number of SCE was counted after two cycles in the presence of BUdR. In cells of the complementation groups A, B, C and D the number of SCE was significantly higher than in UV-exposed control cells. The frequencies of SCE in group E cells and in XP varient cells were not different from those in control cells. Treatment with caffeine (0-200 microgram/ml) did not result in a different response of variant cells compared with normal cells. A simple correlation between SCE frequency and residual excision-repair activity was not observed. The response of the excision-repair deficient cells suggest that unrepaired damage, produced by UVR is involved in the production of SCE.
To characterize the mutations in different unrelated xeroderma pigmentosum (XP) patients, a complementation test was performed using the technique of somatic cell hybridization. DNA repair following UV exposure was studied in multinuclear cells resulting from fusions between in vitro cultivated cells from different patients. The parental XP cells performed low or negligible levels of repair DNA synthesis, whereas in some combinations binuclear hybrid cells showed repair DNA synthesis as a result of complementation. The results indicate the presence of five different complementation groups in XP.
A collaborative study was undertaken to determine the relationship between the three DNA repair complementation groups in xeroderma pigmentosum found at Erasmus University, Rotterdam, and the four groups found at the National Institutes of Health, Bethesda. The results of this study reveal that there are five currently known complementation groups in xeroderma pigmentosum.
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