Validation of the micronucleus-centromere assay for biological dosimetry

Abstract

The micronucleus assay is frequently used for purposes of biological dosimetry. Due to high interindividual variability in the spontaneous frequency of micronuclei, its sensitivity in the low dose region is poor. It has been suggested that this problem can be mitigated by selectively analyzing the frequency of those micronuclei which contain only acentric fragments. Using a pan-centromeric FISH probe we have studied the dose dependence of micronuclei with centromeres in peripheral lymphocytes of human donors. In contrast to previous publications, our approach is based on determining the relative frequency of micronuclei with and without centromeric signals. Our results confirm previous observations that in the low dose range of ionizing radiation, the micronucleus-centromere assay is more sensitive than the conventional micronucleus test.

A semi-automated micronucleus-centromere assay to assess low-dose radiation exposure in human lymphocytes

“…Th ese data are in agreement with previously published data by Vral et al (1997), Th ierens et al (1999b, Wojcik et al (2000) and Pala et al (2008). Vral et al (1997) showed that by manual scoring of centromere-negative micronuclei in 2000 binucleated cells a detection limit of 0.1 Gy (at the 95% confi dence limit) was achieved.…”

“…Th is number of MNCMϩ remains rather constant and only increases slightly after a dose of 1 -2 Gy. Th is fi nding of a high % of MNCMϩ in spontaneous MN is in agreement with previous literature data (Darroudi et al 1996, Huber et al 1996, Vral et al 1997, Wojcik et al 2000, Pala et al 2008 although the percentages of MNCMϩ found in these papers are in general somewhat lower (73 -50%).…”

“…Th e higher MN frequency observed with age and in females compared to males has also been attributed to an increase in MNCMϩ in several literature studies (Th ierens et al 1991, Catalan et al 1998, Fenech 1998, Carere et al 1999, Bolognesi et al 1999, Wojcik et al 2000, Pala et al 2008. Using an X-chromosome specifi c centromeric probe it was shown that the X-chromosome is more often than expected involved in this spontaneously occurring chromosome loss (Catalan et al 1998, Carere et al 1999, Norppa and Falck 2003.…”

Aluminum-induced micronuclei and apoptosis in human peripheral-blood lymphocytes treated during different phases of the cell cycle

“…The analysis was restricted to micronuclei in the vicinity of two main nuclei. The same procedure has been applied previously (Wojcik et al, 2000;Kryscio et al, 2001).…”

Individual variations in the micronucleus assay for biological dosimetry after high dose exposure

“…A problem associated with the Mn test is the relatively large inter-individual variability with respect to the shape of the dose-response-curve for Mn [12][13][14][15]. In their experiments Müller and Rode analysed PBL of only 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.…”