Restitution of chromatid and isochromatid breaks induced in the G2 phase by actinomycin D.

Although actinomycin D (AMD) appears to cause chromatid breakage, it has been suggested that it merely weakens the chromosomal proteins, causing breaks to occur during the stress of fixation. To determine if this was true, we examined lymphocytes treated with AMD (3.5 micrograms/ml) for 90 min prior to harvesting for evidence of DNA repair. Besides single chromatid breaks, we observed a high frequency of chromatid exchange figures (translocations, inversions, rings) and closed isochromatid breaks, indicating that a type of DNA repair leading to chromosome aberration had occurred prior to cell fixation. Therefore, at least some of the breaks observed after AMD treatment in G2 represented true DNA damage and were not merely artifacts of fixation.