Radiation-induced G2 delay and spontaneous chromosome aberrations in ataxia-telangiectasia homozygotes and heterozygotes.
The extent of cell cycle delay of lymphocytes X-irradiated in G2 phase was measured by mitotic inhibition determinations in 66 controls, 14 ataxia-telangiectasia (A-T) homozygotes and 27 obligate heterozygotes. Homozygotes had a significantly reduced mitotic index (MI) in unirradiated samples and showed significantly less radiation-induced mitotic inhibition than controls. This confirms our earlier disputed observations on A-T fibroblasts and demonstrates a G2 check-point defect in addition to the well-known defects in S phase and at the G1-S phase transition. There are two separate and opposite abnormal G2 responses of A-T cells; a primary event in which cells in G2 at the time of irradiation suffer less delay than controls, and a secondary event in which cells irradiated at earlier stages of the cycle are more delayed when they pass into G2. The MI of unirradiated heterozygote cells and the extent of mitotic inhibition were indistinguishable from controls. Spontaneous unstable chromosome aberrations were, as previously reported, significantly higher in homozygotes than in controls. This was true for breaks, but not for gaps. There was a suggestion of an increase in breaks in heterozygotes, but a much larger study would be required to confirm or refute this.
Paterson Institute for Cancer Research, Christie CRC Research Centre, Manchester, UK.
D
D
Scott
A R
AR
Spreadborough
S A
SA
Roberts
D000293:Adolescent; D000328:Adult; D000368:Aged; D001260:Ataxia Telangiectasia / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D016195:G2 Phase / Q000528:radiation effects*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D008938:Mitosis / Q000528:radiation effects; D008940:Mitotic Index; D014965:X-Rays