POSTIRRADIATION DNA-SYNTHESIS INHIBITION AND G(2) PHASE DELAY IN RADIOSENSITIVE BODY CELLS FROM NON-HODGKINS-LYMPHOMA PATIENTS - AN INDICATION OF CELL-CYCLE DEFECTS

In the present study, both post-irradiation DNA synthesis and G(2) phase accumulation were analyzed in lymphoblastoid cell lines (LCLs) and fibroblast cell strains derived from (Saudi) patients with non-Hodgkin's lymphoma (NHL), ataxia telangiectasia (AT), AT heterozygotes and normal subjects. A comparison of the percent DNA synthesis inhibition (assayed by H-3-thymidine uptake 30 min after irradiation), and a 24 h post-irradiation G(2) phase accumulation determined by flow cytometry placed the AT heterozygotes and the NHL patients in an intermediate position between the normal subjects (with maximum DNA synthesis inhibition and minimum G(2) phase accumulation) and the AT homozygotes (with minimum DNA synthesis inhibition and maximum G(2) accumulation). The similarity between AT heterozygotes and the NHL patients with respect to the two parameters studied after irradiation was statistically significant. The data indicating a moderate abnormality in the control of cell cycle progression after irradiation in the LCLs and fibroblasts from NHL patients may explain the enhanced cellular and chromosomal radiosensitivity in these patients reported by us earlier. In addition to demonstrating a link between cell cycle abnormality and radiosensitivity as a possible basis for cancer susceptibility, particularly in the NHL patients, the present studies emphasized the usefulness of the assay for 24 h post-irradiation G(2) phase accumulation developed by Lavin et al. (1992) in characterizing AT heterozygote-like cell cycle anomaly in cancer patients irrespective of whether they carried the AT gene or any other affecting the cell cycle.