Published in Cancer Detection and Prevention 1997; 21(1):91-102.

Kinetics of g1/s and g2/m Transition in X-Irradiated Ataxia-Telangiectasia Cells

Sven Skog PhD1, Rolf Lewensohn MD PhD2, Qimin He PhD1, Anna-Lena Borg1, Richard Gatti MD3

1Department of Medical Radiobiology, Karolinska Institute, Stockholm, Sweden; 2Department of Oncology, Radiumhemmet, Karolinska Hospital and Swedish Radiation Protection Institute, Stockholm, Sweden; 3Department of Pathology, University of California, Los Angeles, School of Medicine, Los Angeles, CA

Address all correspondence and reprint requests to: Sven Skog, PhD, Department of Medical Radiobiology, Karolinska Institute, S-171 76 Stockholm, Sweden.

ABSTRACT: 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 cdc2(p34) 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 is 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.

KEY WORDS: radiosensitivity, cell cycle, p53, cdc2(p34), ataxia-telangiectasia.