The effect of wortmannin on radiation-induced chromosome aberration formation in the radioresistant tumor cell line WiDr.

We analyzed the formation of radiation-induced chromosome aberrations in the cells of the radioresistant colon carcinoma cell line WiDr after treatment with wortmannin, an inhibitor of PI-3 kinases, including DNA-PK. Cells irradiated in G0/G1 phase with 200 kV X rays were treated with wortmannin before or after irradiation. Chromosome-type and chromatid-type aberrations were scored in metaphase cells by either Giemsa staining or FISH. Moreover, DNA-PK activity was measured in the absence and presence of wortmannin. In irradiated G0/G1-phase WiDr cells, only chromosome-type aberrations, including simple and complex exchanges and excess acentrics, were observed. After addition of 1 to 20 microM wortmannin, the formation of chromosome-type exchange aberrations was completely suppressed. The irradiated cells displayed exclusively chromatid-type aberrations including simple and complex chromatid exchanges and chromatid/isochromatid breaks. Whether the chromatid-type aberrations arise during G0/G1 as a result of homologous recombination processes coping with damaged DNA or whether DNA damage induced during G0/G1 phase persists until S and G2 phase and is then processed by homologous recombination pathways must be investigated further.