COMET ASSAY ANALYSIS OF REPAIR OF DNA STRAND BREAKS IN NORMAL AND DEFICIENT HUMAN-CELLS EXPOSED TO RADIATIONS AND CHEMICALS - EVIDENCE FOR A REPAIR PATHWAY SPECIFICITY OF DNA LIGATION

The induction and resealing of DNA strand breaks in a cell. line with a proven defect in DNA ligase I, 46BR, and in two Bloom's syndrome cel l lines, YBL6 and GM 1492, were compared to those observed in normal h uman 1BR/3 fibroblasts after treatment with a variety of genotoxic age nts whose lesions are processed by different repair pathways. This ana lysis was performed using the single-cell gel electrophoresis assay. T he three types of cells were found to have similar capabilities to rec ognize and incise ultraviolet photoproducts and also demonstrated simi lar amounts of DNA breaks immediately after gamma irradiation. During post-treatment incubation, 46BR cells showed a marked DNA re-ligation defect after ultraviolet radiation damage, GM 1492 cells demonstrated a highly reduced DNA joining ability after relatively high doses of ul traviolet radiation, and YBL6 cells were particularly affected in DNA re-ligation after damage by 4-nitroquinoline-1-oxide. The two Bloom's syndrome cell lines and 46BR cells had a nearly normal ability to rese al breaks resulting from gamma irradiation or treatment with xanthine plus xanthine oxidase. These findings suggest that different DNA ligas es may be involved in different DNA repair pathways in human cells. (C ) 1995 by Radiation Research Society