Detection of individual differences in radiation-induced apoptosis of peripheral blood lymphocytes in normal individuals, ataxia telangiectasia homozygotes and heterozygotes, and breast cancer patients after radiotherapy

Quantification of radiation-induced apoptosis in peripheral blood lymphocyt es (PBLs) has been proposed as a possible screening test for cancer-prone i ndividuals and also for the prediction of normal tissue responses after rad iotherapy. We have used the TUNEL assay (terminal transferase nick-end labe ling) 24 h after irradiation with 4 Gy at high dose rate to assess interind ividual differences in radiation-induced apoptosis between (1) a panel of n ormal individuals, (2) ataxia telangiectasia (AT) homozygotes and heterozyg otes, and (3) breast cancer patients who had received radiotherapy 8-13 yea rs ago, including a number of patients who had suffered adverse responses t o radiation. With this protocol, we show clear differences in radiation-ind uced apoptosis between individuals, and good reproducibility in the assay. In agreement with previous reports using EBV-transformed lymphoblasts, we s how a very poor induction of apoptosis in AT homozygotes and a reduced leve l in AT heterozygotes compared to normal individuals. A similar reduced lev el compared to normal individuals was seen in the breast cancer patients. D espite a wide range of values in the breast cancer patients and good reprod ucibility on repeat samples, there was no correlation of rates of apoptosis with the severity of breast fibrosis, retraction or telangiectasia. The re duced rate of apoptosis observed in the breast cancer cases may be associat ed with genetic predisposition to breast cancer; however, we conclude that assays of lymphocyte apoptosis are unlikely to be of use in predicting norm al tissue tolerance to radiotherapy. (C) 2000 by Radiation Research Society .