
INVOLVEMENT OF CHROMOSOMES 7, 18 AND X
IN MITOMYCIN C-INDUCED MICRONUCLEI Hovhannisyan GG1,2*, Mkrtchyan H1,2, Liehr T2, Aroutiounian R1 *Corresponding Author: Dr. Galina G. Hovhannisyan, Department of Genetics and Cytology,
State University, Biological Faculty, 1 Alex Manoukian Street, Yerevan 375025, Armenia; Tel.:
+374-10552354; Fax: +374-10554641; e-mail: hovgalina@list.ru page: 45
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INTRODUCTION
In most eukaryotes including humans, chromosomes are visible and easy to analyze when spread out during metaphase. However, by applying molecular cytogenetics, chromosomes can be visualized, and are arranged so that they do not overlap [1], and keep their shape and general organization in both metaphase and interphase [2-4], but decondensation occurs transversely to the chromosome axis [2,3]. The interphase architecture and possible epigenetic consequences of the chromosomal arrangements within human nuclei are a matter of research and discussion [5,6]. It has been repeatedly demonstrated that some chromosomes (like #19) are centrally localized and others are localized at the nuclear periphery (like #18) [7-11]. These findings have been confirmed for human sperm [11,12].
Micronuclei (MN) are small, extra nuclear bodies that arise in dividing cells from acentric chromosome/chromatid fragments or from whole chromosome/chromatid that lag behind during anaphase and are not included in the daughter nuclei in telophase [13]. The cytokinesis-block micronucleus assay (CBMN) is extensively used for measuring MN in human lymphocytes, and can be considered as a “cytome” assay that allows genotoxic, cytotoxic and cytostatic events to be captured within one assay [14]. Its key advantages are its ability to detect both clastogenic (causing chromosome disruption and breakage) and aneugenic (inducing aneuploidy) events, and to identify cells that have divided once in culture. Its use in combination with the fluorescence in situ hybridization (FISH) technique using centromeric probes, has been developed to distinguish MN induced by chromosomal loss from those originating from chromosome breakage [15]. How MN are formed and which DNA is specifically excluded from the main nucleus is not well understood. We have tested the hypothesis that the chromosomal interphase position is directly related to the involvement of a specific chromosome in the formation of MN. We focused on chromosomes 7, 18 and X which are known to be located more peripherally in the nucleus [12] and differed by their size and levels of condensation (for active and inactive X chromosome).
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