Chromosomal aberrations and in vitro radiosensitivity: intra-individual versus inter-individual variability.

In order to assess the applicability of the micronucleus (MN) and G2 assays as biomarkers of in vitro radiosensitivity and cancer susceptibility, we investigated the inter- and intra-individual variation of these endpoints. For the MN assay unstimulated blood cultures from 57 healthy donors were exposed in vitro to 3.5 Gy Co gamma-rays and for the G2 assay PHA stimulated cultures were irradiated with a dose of 0.4 Gy Co gamma-rays in the G2 phase of the cell cycle. For 14 donors, 2-15 repeat samples were tested over a period of 3 years. The repeat experiments revealed that the intra-individual variability was not significantly different from the inter-individual variability for both G2 and MN assays. As the intra-individual variability determines the reproducibility of the assay, our results highlight the limitations of these endpoints in detecting reproducible differences in radiation sensitivity between individuals within a normal population. Due to the high intra-individual variability and no significant difference with the inter-individual variability found in our study we conclude that care has to be taken when results obtained with chromosomal aberration assays based on one blood sample are used to assess the individual radiosensitivity. Multiple blood sampling may be necessary to draw reliable conclusions. Although more validation studies on the reliability of the G2 and MN assay will be required before they can be used in a confident way as biomarkers of individual radiosensitivity or cancer susceptibility the assays are very valuable to examine population radiosensitivity and the relationship between radiosensitivity, cancer predisposition and genotype.