Abstract
BackgroundMicronucleus (MN) assay is a well standardized approach for evaluation of clastogenic/aneugenic effects of mutagens. Fluorescence in situ hybridization (FISH) is successfully used to characterize the chromosomal content of MN. However, the relationships between nuclear positioning, length, and gene density of individual chromosomes and their involvement in MN induced by different mutagens have not been clearly defined.ResultsChromosomal content of MN was characterized in human leukocytes treated with mitomycin C (MMC) and bleomycin (BLM) by FISH using centromeric (cep) and whole-chromosome painting (wcp) probes. Involvement of chromosomes 8, 15 and 20 in MMC-induced and chromosomes 1, 9 and 16 in BLM-induced MN was studied, and correlated with chromosome size, gene density and interphase position. The results obtained were analyzed together with previous own data on the frequencies of inclusion of chromosomes 3, 4, 6, 7, 9, 16, 17, 18, and X in MMC-induced MN. It could be shown that MMC- and BLM-induced MN could contain material derived from all chromosomes investigated. Involvement of whole chromosomes 8, 15 and 20 in MMC-induced MN negatively correlated with gene density; however, analysis together with earlier studied chromosomes did not confirm this correlation. Inclusion of chromosomes 8, 15 and 20 in MMC-induced MN does not depend on their size and interphase position; the same result was found for the twelve overall analyzed chromosomes. In BLM-treated cells significant correlation between frequencies of involvement of chromosomes 1, 9 and 16 in MN and their size was found.ConclusionsOur results clearly revealed that BLM differs from MMC with respect to the distribution of induced chromosome damage and MN formation. Thus, DNA-damaging agents with diverse mechanism of action induce qualitatively different MN with regard to their chromosomal composition. Also this study demonstrates the utility of combined sequential application of cep and wcp probes for efficient detection of MN chromosomal content in terms of centric and acentric fragments.
Highlights
Micronucleus (MN) assay is a well standardized approach for evaluation of clastogenic/aneugenic effects of mutagens
Number of wcp and cep signals in mitomycin C (MMC)- and BLMinduced MN In the present study we have identified the chromosomes and chromosomal fragments involved in MN induced by MMC and BLM
According to the results obtained 1.6–2.8 times more MN containing wcp than cep signals were detected in MMCtreated cells and 3.5–8.14 times more in cells treated with BLM
Summary
Micronucleus (MN) assay is a well standardized approach for evaluation of clastogenic/aneugenic effects of mutagens. Fluorescence in situ hybridization (FISH) is successfully used to characterize the chromosomal content of MN. Fluorescence in situ hybridization (FISH) is widely used to localize chromosome damage in genetic toxicology [4] and to detect genetic aberrations of medical significance [5]. Fluorescent DNA probes that bind defined genomic sequences are successfully applied to characterize the chromosomal content of spontaneous and mutagen-induced human MN. Random involvement of chromosomes in radiation-induced MN, depending on the DNA content, was shown by [10]. Other studies demonstrated both random and non-random incorporation of DNA from different chromosomes in radiationinduced MN, larger chromosomes being usually overrepresented in the MN content [11, 12]
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