Tigran Harutyunyan

Comparative analysis of individual chromosome involvement in micronuclei induced by mitomycin C and bleomycin in human leukocytes

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.

Asymptotics of the eigenvalues of Sturm-Liouville problem

We prove a new asymptotic formula for the eigenvalues of Sturm-Liouville problem with summable potential. The obtained result extends and make more precise previously known formulas, and takes into account the smooth dependence of the spectral data on boundary conditions.

Influence of aflatoxin B1 on copy number variants in human leukocytes in vitro

BackgroundAflatoxin B1 (AFB1) is a mycotoxin produced by Aspergillus spec. The latter are worldwide contaminants of food with mutagenic and carcinogenic activities in animals and humans. AFB1 was shown to have deleterious effects on metabolism of eukaryotes in many model systems, including the ability to inhibit DNA replication. An agent that disturbs DNA replication may also have the potential to induce de novo DNA copy number variations (CNVs).ResultsBlood samples of three clinically healthy carriers were treated in vitro with AFB1 and chromosome preparations were subjected to parental origin determination fluorescence in situ hybridization (pod-FISH). Probes able to visualize CNVs in 8p21.2 and 15q11.2 were applied. In this setting here for the first time an influence of AFB1 on molecular-cytogenetically detectable CNVs could be shown.ConclusionsThe obtained results indicate that: (i) pod-FISH is a single cell directed, sensitive and suitable method for the analysis of mutagen induced CNVs, (ii) AFB1 has the potential to induce in vitro instability of known CNVs in human leukocytes.

Isospectral Dirac operators

We give the description of self-adjoint regular Dirac operators, on

Micronuclei and What They Can Tell Us in Cytogenetic Diagnostics

[0, \pi]

On the norming constants of the Sturm-Liouville problem

, with the same spectra.

Effect of Glutathione S-transferase mu 1 (GSTM1) gene polymorphism on chronic myeloid leukemia risk and Imatinib treatment response

Purpose of ReviewThe micronucleus (MN) assay is a validated method of genetic toxicology, widely used for human biomonitoring studies. This review summarizes and discusses current data regarding involvement of MN in pathogenesis of different diseases, potential of MN assay to be used as cytogenetic diagnostic technique, as well as highlights current achievements in studies concerning clinically relevant chromosomal instability using MN assay.Recent FindingsRecent studies suggested that MN are indicator of pathological events in affected as well as not affected “target” tissues of an organism. They can be effectively used in risk assessment and to distinguish stage of pathological manifestations in diseases. Molecular-genetic studies revealed that MN are not only the markers of, but at the same time inducers of genomic instability.SummaryThe MN assay is an informative cytogenetic tool, alone and in combination with molecular genetic methods. Although it is not always clear if MN are a result or inducer of pathogenic effects, the vast number of clinical studies substantiated that they have high potential for clinical practice, as they are associated with diseases.