title: Comparative analysis of individual chromosome involvement in micronuclei induced by mitomycin C and bleomycin in human leukocytes.
abstract: BACKGROUND
  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. 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.
  
  
  RESULTS
  Chromosomal 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Genetics and Cytology, Faculty of Biology, Yerevan State University, 1 Alex Manoogian, 0025 Yerevan, Armenia.
authors.forename: Galina
authors.identifier: 0000-0002-7450-1508
authors.initials: G
authors.lastname: Hovhannisyan
authors.affiliation: Department of Genetics and Cytology, Faculty of Biology, Yerevan State University, 1 Alex Manoogian, 0025 Yerevan, Armenia.
authors.forename: Rouben
authors.initials: R
authors.lastname: Aroutiounian
authors.affiliation: Department of Genetics and Cytology, Faculty of Biology, Yerevan State University, 1 Alex Manoogian, 0025 Yerevan, Armenia ; Institute of Molecular Biology, National Academy of Sciences, 7 Hasratyan, 0014 Yerevan, Armenia.
authors.forename: Nelly
authors.initials: N
authors.lastname: Babayan
authors.affiliation: Department of Genetics and Cytology, Faculty of Biology, Yerevan State University, 1 Alex Manoogian, 0025 Yerevan, Armenia.
authors.forename: Tigran
authors.initials: T
authors.lastname: Harutyunyan
authors.affiliation: Jena University Hospital, Friedrich Schiller University, Institute of Human Genetics, Kollegiengasse 10, D-07743 Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
keywords: Bleomycin; Chromosome; FISH; Human leukocytes; Micronuclei; Mitomycin C