Genetic determination of chromosomal radiosensitivities in G0- and G2-phase human lymphocytes

The radiosensitivity of human lymphocytes measured using a G0- or G2-assay has been linked with an individual's risk of developing normal tissue complications following radiotherapy. This study was performed to increase basic knowledge of the genetics of the human radiation response, and chromosomal aberration induction in particular.

The study was carried out with blood samples taken from 15 monozygotic twin pairs. G0-assay was performed for cells irradiated with 6 Gy counting only deletions and G2-assay for cells irradiated with 0.5 Gy scoring only chromatid breaks.

The mean number of deletions measured at 6 Gy for all 30 samples using the G0-assay amounted to 2.96+/-0.37 (means+/-SD), which corresponds to a coefficient of variation (CV) of 13%. There is a highly significant intra-pair correlation for this number among twins (r(2)=0.911) demonstrating that this parameter is mostly determined by genetic factors. According to the mean number of deletions, a theoretical classification based on the definition < or = MV-SD as resistant, MV+/-SD as normal and > or = MV+SD as sensitive was made, identifying two pairs as sensitive or resistant, respectively, while nine were normal and two pairs are intermediate. For chromatid breaks measured at 0.5 Gy with the G2-assay the mean number was 1.35+/-0.42 (means+/-SD) corresponding to a CV of 31%. There was again a strong intra-pair correlation among twins with r(2)=0.837 showing that this sensitivity is also determined mostly by genetic factors. There was, however, no inter-assay correlation between the G0- and G2-sensitivity (r(2)=0.006) demonstrating that these two sensitivities depend on different genetic factors.

The chromosomal radiosensitivity of lymphocytes as defined by G0- or G2-assay is largely determined by different genetic factors, which may allow the use of genetic profiling as an indicator of the respective individual radiosensitivity.