Cytogenetic evidence for differences in DNA incision activity in xeroderma pigmentosum group A, C and D cells after...

The capacity of cells to incise DNA to remove altered sites after DNA damage can be determined from the rate of DNA-strand break accumulation in the presence of an inhibitor of DNA-repair synthesis, such as 1-beta-D-arabinofuranosylcytosine (ara-C). Because each chromatid contains a single continuous molecule of double-stranded DNA, chromatid breaks and gaps, i.e., non-displaced breaks, represent unrepaired DNA-strand breaks. The accumulation of chromatid breaks and gaps after X-irradiation in the presence of ara-C thus provides a measure of DNA incision activity. Addition of ara-C to skin fibroblasts or stimulated blood lymphocytes from normal individuals at intervals after X-irradiation significantly increased frequencies of chromatid breaks and/or gaps. In contrast, addition of ara-C to XP cells of complementation groups A and D had a negligible effect and a significant but less than normal effect on XP cells of complementation group C and one sample of blood lymphocytes of undetermined complementation group. The results thus show negligible incision activity after G2 phase X-irradiation in XP-A and XP-D cells and a level higher but less than normal in XP-C cells.