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.
Virsik-Köpp
Patricia
P
Abteilung für Umweltmedizin und Hygiene, Medizinische Fakultät, Georg-August-Universität Göttingen, D-37075 Göttingen, Germany. patricia.virsik@medizin.uni-goettingen.de
Hofman-Hüther
Hana
H
Rave-Fränk
Margret
M
Schmidberger
Heinz
H
D000730:Androstadienes / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations / Q000187:drug effects / Q000528:radiation effects*; D003110:Colonic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D004249:DNA Damage; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase; D006801:Humans; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D011836:Radiation Tolerance; D016192:Resting Phase, Cell Cycle; D000077191:Wortmannin
D000730:Androstadienes; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D000077191:Wortmannin