The micronucleus and G2-phase assays for human blood lymphocytes as biomarkers of individual sensitivity to ionizing radiation: limitations imposed by intraindividual variability.

As part of a program to assess the applicability of the micronucleus (MN) and G2-phase assays as biomarkers of cancer susceptibility, we investigated the inter- and intraindividual variations of these end points. For the MN assay, unstimulated blood cultures from 14 healthy donors were exposed in vitro to 3.5 Gy 60Co gamma rays; for the G2-phase assay, PHA-stimulated cell cultures were irradiated with a dose of 0.4 Gy 60Co gamma rays in the G2 phase of the cell cycle. Two of the 14 volunteers were assayed 9 times over a period of 1 year. The repeat experiments revealed that the intraindividual variability was not significantly different from the interindividual variability for both the G2-phase and MN assays. Since the intraindividual variability determines the reproducibility of the assay, our results highlight the limitations of these end points in detecting reproducible differences in radiation sensitivity between individuals within a normal population. For example, one donor of the population was identified as being radiosensitive (based on the 90th percentile criterion) but turned out to be normal when the assay was repeated twice. We conclude that the determination of individual radiosensitivity with these two cytogenetic assays is unreliable when based on one blood sample.