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, wh ich evaluates the dynamics of cell cycle traverse. We compared five hu man lymphoblastoid cell lines (LCLs) from A-T homozygotes belonging to complementation group A (ARO, BRO, RJO) and group C (CSA, BMA) with t hree cell Lines from healthy volunteers (KK-B2, MTB, HGL). The A-T cel l 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 do se-dependent pattern, while the A-T cells did not arrest in G1 until a fter 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 descr ibed by others. In respect to G2 arrest, A-T cells from complementatio n group C (CSA, BMA) arrested to the same extent as cells from healthy volunteers. On the other hand, the other LCLs from complementation gr oup A arrested normally, while cells from ARO and BRO did not arrest i n G2. The lack of G2 arrest in BRO cells was accompanied by unchanged cdc2(p34) activity. In summary, a defective radiation-induced G1 arres t seems to be present in both complementation groups of A-T homozygote s, 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.