INCREASED RADIOSENSITIVITY AND RADIORESISTANT DNA-SYNTHESIS IN CULTURED FIBROBLASTS FROM PATIENTS WITH CORONARY ATHEROSCLEROSIS

Cultured skin fibroblasts from five patients with atherosclerosis who underwent coronary artery bypass graft surgery were compared with thos e from one ataxia telangiectasia (AT) homozygote, three AT heterozygot es, and five healthy subjects to determine their sensitivity to gamma radiation as determined by a colony survival assay. Fibroblasts from f our of these patients were also compared with those from two AT homozy gotes, two AT heterozygotes, and three healthy subjects to determine p ostirradiation [H-3]thymidine incorporation, indicating the levels of radioresistant DNA synthesis (RDS). On the basis of colony survival as say, after long-term irradiation (at low dose rate, ie, 0.007 Gy/min), fibroblasts from all five patients with atherosclerosis exhibited rad iosensitivity that was intermediate between that of the healthy subjec ts and that of patients with the known radiosensitive syndrome AT. How ever, there was a considerable interstrain difference in the radiosens itivity of fibroblasts from patients with atherosclerosis, with their mean D-10 values (radiation dose resulting in 10% cell survival) varyi ng between 2.3 and 6.2 Gy, whereas the mean D-10 values for the cells from the AT homozygote, AT heterozygotes, and healthy subjects were 2. 0, 3.8, and 9.0 Gy, respectively. One of the patients with atheroscler osis showed cellular radiosensitivity quite similar to that of the AT homozygote, up to 2% to 10% of survival levels after short- (at a dose rate of 8 Gy/min) and long-term irradiation, respectively The results of [H-3]thymidine incorporation showed an AT heterozygote-like RDS in fibroblasts from patients with atherosclerosis that appeared to be in termediate between that of AT homozygotes and that of healthy subjects , suggesting a partial deregulation of cell cycle in the patients with atherosclerosis. Overall, the results suggest that increased cellular radiosensitivity and/or altered cell cycle regulation may be associat ed with atherosclerosis.