Chromosome content and ultrastructure of radiation-induced micronuclei

Abstract

Unrepaired or misrepaired radiation damage in mammalian chromosomes can result in micronucleus formation at the first cell division. This represents loss of genomic information which may cause cell death. To improve our understanding of the mechanism of radiation-induced micronucleus formation, we characterized micronucleus ultrastructure and identified the origin of micronucleus DNA. Immunofluorescence microscopy showed that micronuclei were structurally similar to main nuclei since they contained nuclear lamins A and C and were encapsulated by a network of vimentin intermediate filaments. The contents of radiation-induced micronuclei were characterized using fluorescence in situ hybridization to probe for DNA originating from chromosomes 2, 7, 11 and 16. We postulated that if incorporation of DNA into micronuclei were random, then the probability of chromosomal DNA in micronuclei would be related to the target, i.e. chromosome size. Our results demonstrated that incorporation of DNA from smaller chromosomes (11 and 16) was not different from expected values but incorporation of DNA from the larger chromosomes (2 and 7) was significantly greater than expected. Not all chromosomes in the human genome, therefore, were equally susceptible to genomic loss by micronucleus encapsulation. In conclusion, radiation-induced micronuclei have similar structural characteristics to main nuclei, chromosome damage and/or repair after ionizing radiation may be non-random, and micronucleus formation may reflect this variability.

Influence of novobiocin on <FONT FACE=Symbol>g</font>-irradiation G0-lymphocytes as analyzed by cytogenetic endpoints

“…Therefore, the absence of correlation between CA and MN frequencies observed in our study is in accordance with the following evidence: some specific types of CA may form MN in preference to other aberrations (Wakata and Sasaki, 1987), multiple fragments may reside within a single MN (Jonhston et al, 1997) and a considerable percentage of MN may have originated from whole chromosomes due to disturbance of the cell spindle (Walker et al, 1996). According to Johnston et al (1997), the interactions between the initial damage, repair processes, cell cycle-dependent variations in sensitivity and changes in cell kinetics can produce complex patterns of MN expression.…”

Induced Nuclear Pleomorphism in Pollen Mother Cells of <i>Crotalaria juncea</i> L. (Sunnhemp)

“…Even though their onset may be wholly spontaneous (Heddle et al 1983), their manifestation is a po- tent index of genotoxicity. Their incidence corroborates both clastogenic and aneugenic (Walker et al 1996, Van Goethem et al 1997, Hayashi et al 1998, Fenech et al 2003 implications of mutagens. Chromosomal breaks validate the former, while spindle inactivation substantiates the latter.…”

CtBPs Promote Cell Survival through the Maintenance of Mitotic Fidelity

“…3E). As a control, we used ionizing radiation to cause DNA breaks, as ϳ85% of radiation-induced micronuclei arise from acentric chromosome fragments (57). Less than 20% of the micronuclei formed in irradiated MCF-7 cells stained positive for CENP-A.…”