How reliable are chromosomal aberration assays as bio markers of individual towards ionising radiation?

Full text: Biomarkers of susceptibility or sensitivity towards ionising radiation can be important for the identification of individuals that may be at increased risk for the development of cancer after occupational, environmental or medical exposures. It is essential that these biomarkers have certain traits in order to be effective indicators of sensitivity. They should be specific, sensitive and reliable. Possible candidates for biomarkers of radiosensitivity are chromosomal aberrations. It has been shown that the induction of chromatid aberrations after irradiation of lymphocytes in G2 phase of the cell cycle and the induction of MN after irradiation in Go both allow discrimination between normal individuals and patients with cancer prone genetic diseases. In this study we investigated the inter- and intra- individual variation of the MN assay and the G2 assay in irradiated lymphocytes to assess their suitability as biomarkers of susceptibility. For this, the G2 assay and the MN assay were performed on blood samples of 10 healthy individuals. For the MN assay Go lymphocytes were exposed to 3.5 Gy Co γ-rays either at high dose-rate (HDR) and stimulated immediately or with 6h delay (DS) or at low dose-rate (LDR). For the G2 assay lymphocytes were irradiated with a dose of 0.4 Gy Co γ-rays in G2 phase of the cell cycle. Two individuals were assayed 9 times each in nine different experiments over a time period of 1 year. All samples were analysed by 2 scorers and no significant differences between them were observed using a paired t-test. The repeat experiments on blood samples of the same donor revealed that the inter-experimental/intra-individual coefficients of variation were not significantly different from the inter-individual coefficients of variation in both G2 and MN assay. As the intra-individual variability determines the assay reproducibility this would indicate that the assays are not able to detect real, reproducible differences in radiation sensitivity between normal individuals in the population. The repeat experiments further revealed that for some healthy donors a high value, defined as sensitive taking the 90th percentile as cut-off point to define sensitivity, is obtained only at one time point while the values obtained at the other time points were within the normal range (non-sensitive). Based on this one time point the individual would have been regarded as sensitive. To conclude, our results show that a chromosomal aberration assay based on one blood sample may lead to erroneous conclusions with respect to the individual radiosensitivity of workers. (author)