[Features of cytogenetic changes in the human lymphoma U-937 cells after induction of apoptosis by tumor necrosis factor].

A comparative analysis of the frequency of cytogenetic abnormalities in cell population U-937 in control conditions and after exposure to tumor necrosis factor has been performed. We have found that in such treatment there is a maximum effect after 48 h, which is expressed in the stimulation of apoptosis and the accumulation of cells with micronuclei and binuclear cells. The induction of premature chromosome condensation is an early marker of the TNF influence. Changing the composition of the population by the number of chromosomes in the cell may lead to the emergence of a subline with new properties compared to the parental cell population.

[Complexes of antiparallel telomeric G-quadruplex d(TTAGGG)4 with carboxymethyl tetracationic porphyrins].

Porphyrins comprise a chemical class widely used in drug design. Cationic porphyrins may bind to DNA guanine quadruplexes. We report the parameters of binding of 5,10,15,20-tetrakis(N-carboxymethyl-4-pyridinium)porphyrin (P1) and 5,10,15,20-tetrakis(N-etoxy-carbonylmethyl-4-pyridinium)porphyrin (P2) to antiparallel telomeric G-quadruplex formed by d(TTAGGG)4 sequence (TelQ). The binding constants (K(i)) and the number of binding sites (N(i)) were determined from absorption isotherms generated from absorption spectra of complexes of P1 and P2 with TelQ. Compound P1 demonstrated a high affinity to TelQ (K1 = (40 +/- 6) x 10(6) M(-1), N1 = 1; K2 = (5.4 +/- 0.4) x 10(6) M(-1), N = 2). In contrast, the binding constants of P2-TelQ complexes (K1 = (3.1 +/- 0.2) x 10(6) M(-1), N1 = 1; K2 = (1.2 +/- 0.2) x x 10(6) M(-1), N2 = 2) were one order of magnitude smaller than the respective values for P2-TelQ complexes. Measurements of quantum yield and fluorescence lifetime of drug-TelQ complexes revealed two types of binding sites for P1 and P2 on the quadruplex oligonucleotide. The 'strong' complexes can result from interaction of the porphyrinswith TTA loops whereas the weaker complexes are formed with G-quartets. The altered TelQ conformation detected by circular dichroism spectra of P1-TelQ complexes can be explained by a disruption of a G-quartet. We conclude that peripheral carboxy groups contribute tothe high affinity of P1 for the antiparallel telomeric G-quadruplex.

[Interrelationship between polymorphic markers of methylenetetrahydrofolate reductase gene and development of acute disturbance of brain circulation in families of patients with atrial fibrillation].

In the present work we for the first time on the clinic-genetic material revealed genetic predictors of development of acute disturbance of brain circulation (ADBC) in families of patients with atrial fibrillation (AF) namely polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Genotype CC was significantly more often found among patients with AF and ADBC compared with controls (58.1 and 35.2%, respectively, p=0.02) as well as in relatives of probands compared with the control group (59.3 and 35.2%, respectively, p=0.008). With this in relatives with revealed paroxysmal AF and ADBC we also noted presence of CC genotype. Taking into consideration the relationship obtained between polymorphysms of MTHFR gene and AF it was possible to assume that polymorphic marker CC appeared to be a predictor of ADBC in these families.

Karyotype alterations in human lung adenocarcinoma cells after long-term action of interferon-alpha.

AIM: To estimate the effect of long-term IFN treatment of human non-small-cell lung cancer cell line A-549 on their karyotype characteristics and on the clonal structure of cell population. METHODS: Cytogenetic research was performed by standard methods using routine and differential staining. Cytogenetic characteristics were estimated per 1000 cells (ppm, (per thousand)). RESULTS: Cytogenetic analysis of IFN-modified A-549 human lung cancer cells had demonstrated far-going changes in their population structure. It was shown that long term cultivation with IFN altered the chromosome modal class of A-549 cells, induced the domination of hromosomes with certain molecular markers: the number of metaphases with der (6) t (6; 1) chromosomal rearrangement increased significantly (from 6% to 80%, p CONCLUSION: Long-term IFN effect results in alterations of cytogenetic properties of A-549 human lung cancer cells.

[Cytogenetic abnormalities in mammalian somatic cells].

The different types of cytogenetic abnormalities are considered which are used in classic cytogenetics for the estimation of the levels of chromosome apparatus damages. The possible causes of cytogenetic anomalies and a number of methods of micronucleus tests are discussed. It was shown that the different levels of genetic material organization influence the realization of DNA defects into cytogenetic abnormality.

Spontaneous premature condensation of chromosomes in normal and transformed mammal cells.

AIM: To study the relation between premature chromosome condensation and the ability of the cells to undergo malignant transformation. METHODS: Standard cytogenetic analysis of bone marrow cells and cultured normal and tumor cells has been used. RESULTS: Comparative analysis of the frequency of occurrence of the cells with premature chromosome condensation (PCC) (cell "arrest" at G2/M phase) in relation to dividing cells in the cultures of human immortalized cells of hematopoietic origin, human lung carcinoma A-549 cells, and in populations of bone marrow cells of BALB/c and C57BL/6 mice differing in predisposition for myeloma development has been performed. It has been revealed that in populations of bone marrow cells of C57BL/6 mice the relation of cells with PCC to dividing ones is 2-3-fold lower than in other studied cell populations. Immortalized and malignantly transformed human cell lines were characterized by high frequency of occurrence of cells with PCC. In the cells of A-549R subline characterized by suppressed malignant phenotype this index was lower than in parental A-549 cells. CONCLUSION: The obtained data point on possible relation between disturbed passing of "check point" by cells upon transition from G2 phase of cell cycle to mitosis and increased genetic heterogeneity of new cell generation associated with ability of cells to immortalization and malignant transformation.

[Spontaneous mutagenesis in bone marrow cells in the CBA and CBA/H-T6 mouse strains].

Comparative analysis of cytogenetic characteristics in bone marrow cells of the mouse lines CBA and CBA/H-T6 has been carried out. It was shown that translocation T6 effects the apparatus of cell division and can cause additional cytogenetic abnormalities.

[The possible ways of the diploidization of the polyploid germinative stem cells in the mouse BALB/c line].

Quantitative and qualitative chromosome rearrangements in the cell line G1 established from a genital ridge of the 12,5 dpc BALB/c mouse embryo were analysed. Cytogenetic analysis was performed on the 75th passage of in vitro cultivation. It has been shown that by this passage the cell population was heterogenous. It is suggested that such heterogeneity may be caused by realization of two simultaneous processes namely the cell polyploidization and their secondary diploidization. These processes were accompanied by some chromosome destructions, and the creation of small new acrocentric chromosomes and large aberrant chromosomes as well as Robertsonian translocations. The present study demonstrates in vitro karyotype evolution of the mouse cell line G1 including the increased instability of the chromosome apparatus.