Validation of the micronucleus assay for biological dosimetry after high dose exposure

Abstract

The micronucleus assay is widely used as a biological dosimeter. Due to an inhibitory effect of radiation on cell proliferation the assay yields satisfactory results only when the absorbed dose is below about 5 Gy. In 2002 Müller and Rode suggested that a modified version of the test, based on the analysis of the ratio of trinucleated to tetranucleated cells and the frequency of micronuclei (Mn) in binucleated cells containing at least one Mn, can be applied to detect a dose reaching 15 Gy (Mutat. Res. 502:47-51). Their conclusion was based on the results of experiments with lymphocytes from one donor and nothing is known about the possible influence of individual variability on the applicability of the Mn test to detect high doses of radiation. The aim of the present study was to validate the modified micronucleus assay with lymphocytes of 5 donors. Their blood was exposed to 0, 5, 10, 15 and 20 Gy of 60Co gamma rays. The levels of Mn and of cell proliferation were assessed using various approaches. A strong interindividual variability was observed for all endpoints. The results clearly show that the assessment of cell proliferation is essential for the interpretation of results. Unfortunately, it was not possible to identify one single proliferation marker that gives all necessary information. 44

Investigation of DNA Damage and Cell-Cycle Distribution in Human Peripheral Blood Lymphocytes under Exposure to High Doses of Proton Radiotherapy

“…The extent of the effect does depend on the dose, donor, and type of DNA damage. These differences in the amount of DNA damage in HPBLs have been seen in several studies comparing healthy donors and cancer patients [8,19]. The same received dose may result in dissimilar cytotoxic and genotoxic effects.…”

“…The PCC method was applied as a reliable tool for assessing radiation-induced damage and cell-cycle perturbations after high doses of irradiation [16,17]. The assessment of high-radiation doses by biological methods is difficult, due to the inhibitory effect of radiation on cell proliferation [19]. The PCC method provides insights into the mechanisms of chromosome condensation, and the fact that PCC can be induced in cells within minutes after irradiation was recognized as a valuable tool for investigations in chromosome dynamics and kinetics [20].…”