Kinetics of G1/S and G2/M transition in X-irradiated ataxia-telangiectasia cells.
Cell cycle transition defects of homozygous ataxia-telangiectasia (A-T) cells were studied by using a cell cycle flow calculation method, which evaluates the dynamics of cell cycle traverse. We compared five human lymphoblastoid cell lines (LCLs) from A-T homozygotes belonging to complementation group A (ARO, BRO, RJO) and group C (CSA, BMA) with three cell lines from healthy volunteers (KK-B2, MTB, HGL). The A-T cell lines ARO and BRO were derived from the same family. Cell growth and cell cycle traverse were followed for 72 h after X-irradiation with 1-6 Gy. LCLs from healthy volunteers immediately arrested in G1 in a dose-dependent pattern, while the A-T cells did not arrest in G1 until after 12 to 24 h. The time for the appearance of the G1 arrest of these cells was independent of complementation group. The delayed G1 arrest seen in the A-T cells paralleled a lack of induction of p53, as described by others. In respect to G2 arrest, A-T cells from complementation group C (CSA, BMA) arrested to the same extent as cells from healthy volunteers. On the other hand, the other LCLs from complementation group A arrested normally, while cells from ARO and BRO did not arrest in G2. The lack of G2 arrest in BRO cells was accompanied by unchanged cdc2p34 activity. In summary, a defective radiation-induced G1 arrest seems to be present in both complementation groups of A-T homozygotes, whereas a defective G2 arrest in not always observed. The defective G1 arrest seen in A-T cells may play an important role in tumor cell survival after exposure to therapeutic irradiation.
Skog
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Department of Medical Radiobiology, Karolinska Institute, Stockholm, Sweden.
Lewensohn
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Borg
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Gatti
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D001260:Ataxia Telangiectasia / Q000473:pathology*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D016193:G1 Phase / Q000528:radiation effects; D016195:G2 Phase / Q000528:radiation effects; D006801:Humans; D008677:Metaphase / Q000528:radiation effects; D008938:Mitosis / Q000528:radiation effects*; D016196:S Phase / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016159:Tumor Suppressor Protein p53; D016203:CDC2 Protein Kinase