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At least 19 recordsLinked to original sources

Relationship between radiation induced adaptive response in human fibroblasts and changes in chromatin conformation.

Chromatin conformation changes in the normal human fibroblasts VH-10 were studied by the method of anomalous viscosity time dependence (AVTD). Gamma-irradiation of cells in a dose range of 0.1-3 Gy caused an increase in maximal viscosity of cell lysates. Conversely, irradiation of cells with low doses of 0.5 or 2 cGy resulted in a decrease in the AVTD peaks with a maximum effect approximately 40 min after irradiation. The same exposure conditions were used to study a possible adaptive effect of low doses, measured by changes in cell survival. A primary dose of 2 cGy caused significant modification of cell response to a challenge dose. Approximately 20% protection to challenge doses of 0.5 Gy (p < 0.003), 2 Gy (p < 0.02) and 2.5 Gy (p < 0.002) was observed. However, the direction of this effect (adaptation or synergism) was found to be dependent on a challenge dose. The combined effect of 2 cGy and 1 Gy was significantly synergistic, while no modification was observed for 1.5 Gy and 3 Gy. A partial correlation was found between the AVTD changes and cell survival when the combined effect of a primary dose of 2 cGy and challenge dose was examined. The dose of 2 cGy alone increased survival by 16% (p < 0.0003). These results suggest that the low-dose induced effects on survival may be related to chromatin reorganization.

Adaptation, Physiological↗

Chromatin conformation modulates repair of single strand interruptions by polynucleotide ligase-[3H] AMP.

Conformationally distinct chromatin populations were utilized as substrates to quantitate the relative amount of and accessibility of internal 5'-phosphomonoester breaks in DNA-chromatin. In these studies, a constant amount of chromatin as well as deproteinized DNA derived from the respective chromatin sample was titrated with increasing quantities of adenylated polynucleotide ligase intermediate. This enzyme intermediate releases its AMP moiety while repairing a DNA single strand interruption, release of AMP being directly proportional to the number of internal 5'-phosphomonoester breaks repaired. Results of this study indicate that the ability of polynucleotide ligase to repair DNA breaks within chromatin was affected by the conformational state of the chromatin. The degree of conformational constraint present in a given chromatin, therefore, determined the capacity of the enzyme to repair internal DNA 5'-phosphomonoester breaks.

Adenosine Monophosphate↗

DNA methylation induced changes in chromatin conformation of the promoter of the vitellogenin II gene of Japanese quail during aging.

One approach to the understanding of the molecular basis of aging in higher organisms may be to use genes whose timing and rate of expression during the life span run parallel with specific functions that can be monitored. The genes for egg proteins, such as vitellogenin (VTG), which is expressed in the liver, and ovalbumin, lysozyme etc. that are expressed in the oviduct of birds, meet these requirements. Egg laying function is dependent on the production of these proteins, which, in turn, depends on the expression of their genes. In this communication we present the age-related studies on the VTG II gene of the bird, Japanese quail. The gene is expressed only in the liver and its expression is considerably lower in old birds that do not lay eggs. Comparison of the promoter region of the gene carrying the two important cis-acting elements, estrogen responsive element (ERE) and progesterone responsive element (PRE), shows it to be 100% homologous to the corresponding region of the chicken VTG II gene. Methylation of DNA and conformation of chromatin of this region were studied, as they are known to be important for regulation of expression of genes. Our studies show that in the liver of adult female quails which lay eggs, a -CCGG- sequence located in this region is hypomethylated, and the chromatin encompassing this region of the gene is relaxed. In the old, the -CCGG- sequence is hypermethylated and the chromatin is compact. This is correlated with a decrease in the expression of the gene and decrease in egg production. Further, electrophoretic mobility shift assay (EMSA) shows that the levels/affinity of specific trans-acting factors that bind to ERE and PRE present in the region, are not different in adult and old birds. Hence the methylation status of the -CCGG- sequence that is located in-between the ERE and the PRE may be crucial for the conformation of chromatin and availability of these two important cis-acting elements for the binding of the trans-acting factors. This, in turn, may downregulate the expression of the gene in old birds.

Aging↗

Nuclear volume and chromatin conformation of small and large bovine luteal cells: effect of gonadotropins and prostaglandins and dependence on luteal phase.

Change in nuclear volume and chromatin conformation are generally considered to reflect altered gene expression in eukaryotic cells. The present studies were undertaken to investigate whether these nuclear parameters of luteal cells can be altered by hormone treatment in vitro or change during the estrous cycle. The nuclear volume of small luteal cells was significantly lower than that of large luteal cells during the cycle and pregnancy. The nuclear volumes of small and large luteal cells from pregnancy did not change during incubation without any hormone or with 10 nM prostaglandin (PG)F 2 alpha. However, incubation with 1 nM human chorionic gonadotropin (hCG) or 10 nM PGE1 resulted in a significant increase of nuclear volume of small luteal cells by 4 h and that of large luteal cells by 6 h. Small luteal cells were more responsive to hCG than large luteal cells. The nuclear volumes of small and large luteal cells also significantly increased from early to mid luteal phase with no further change in late luteal phase. hCG and PGE1, as well as PGF2 alpha, treatment resulted in a change of chromatin conformation of small and large luteal cells. Dibutyryl cyclic AMP (10 mM) mimicked the hormones by increasing nuclear volumes and changing the chromatin conformation of small and large luteal cells. Chromatin conformation of small and large luteal cells also changed from early to mid luteal phase and mid to late luteal phase. In conclusion, in vitro, hCG and PGs can regulate nuclear volume and/or chromatin conformation of small as well as large bovine luteal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗

Regional hypermethylation and global hypomethylation are associated with altered chromatin conformation and histone acetylation in colorectal cancer.

Regional DNA hypermethylation and global DNA hypomethylation are 2 epigenetic alterations associated with colorectal cancers. However, their correlation with microsatellite instability (MSI) and chromosomal instability (CIN) in colorectal cancer, and their relationship with chromatin conformation and histone modification are not clear. In this study, we analyzed regional and global methylation in 16 cell lines and 64 primary colorectal cancers. We found that MSI and CIN are 2 alternative events in most cell lines and tumors. Furthermore, regional hypermethylation and global hypomethylation are also alternative events in most cases. We also observed a strong correlation between MSI and regional hypermethylation and between CIN and global hypomethylation. We further analyzed chromatin conformation and histone acetylation in cell lines with CIN or MSI. CIN cancers had open chromatin conformation and enriched histone acetylation in repetitive as well as in gene-specific regions. MSI cancers, on the other hand, had closed chromatin conformation and low levels of histone acetylation. After a MSI cell line was treated with 5-aza-2'-deoxycytidine or trichostatin A, the closed chromatin conformation became open, and histone acetylation was enriched. These observations support our hypothesis that in colorectal cancer, regional hypermethylation and global hypomethylation are associated with altered chromatin conformation and histone acetylation, which might have a causal correlation with MSI and CIN, respectively.

Acetylation↗

Exposure of rat brain to 915 MHz GSM microwaves induces changes in gene expression but not double stranded DNA breaks or effects on chromatin conformation.

We investigated whether exposure of rat brain to microwaves (MWs) of global system for mobile communication (GSM) induces DNA breaks, changes in chromatin conformation and in gene expression. An exposure installation was used based on a test mobile phone employing a GSM signal at 915 MHz, all standard modulations included, output power level in pulses 2 W, specific absorption rate (SAR) 0.4 mW/g. Rats were exposed or sham exposed to MWs during 2 h. After exposure, cell suspensions were prepared from brain samples, as well as from spleen and thymus. For analysis of gene expression patterns, total RNA was extracted from cerebellum. Changes in chromatin conformation, which are indicative of stress response and genotoxic effects, were measured by the method of anomalous viscosity time dependencies (AVTD). DNA double strand breaks (DSBs) were analyzed by pulsed-field gel electrophoresis (PFGE). Effects of MW exposure were observed on neither conformation of chromatin nor DNA DSBs. Gene expression profiles were obtained by Affymetrix U34 GeneChips representing 8800 rat genes and analyzed with the Affymetrix Microarray Suite (MAS) 5.0 software. In cerebellum from all exposed animals, 11 genes were upregulated in a range of 1.34-2.74 fold and one gene was downregulated 0.48-fold (P < .0025). The induced genes encode proteins with diverse functions including neurotransmitter regulation, blood-brain barrier (BBB), and melatonin production. The data shows that GSM MWs at 915 MHz did not induce PFGE-detectable DNA double stranded breaks or changes in chromatin conformation, but affected expression of genes in rat brain cells.

Animals↗

Sex-specific alterations in chromatin conformation of the brain of aging mouse.

Chromatin conformation has been analysed in the brain cortex of adult (24+/-2 weeks) and old (65+/-4 weeks) male and female mice. Nuclei purified from different groups of mice were digested with MNase and DNase I for varying time periods (0-90 min), and with endogenous endonucleases for 1 h. MNase and DNase I digestion kinetics showed that the percentage of acid solubility of chromatin was relatively lower in old than adult and in female than male. This was further supported by electrophoretic analysis of nuclease digested DNA fragments. When the nuclei were incubated with only Ca2+ or Mg2+, no endonuclease digestion was observed. However, under similar conditions, the liver DNA was cleaved substantially. When divalent cations were added together, they activated endogenous endonucleases and digested the brain chromatin. The activity of Ca2+/Mg2+-dependent endogenous endonucleases was higher in male than female. Thus the accessibility of chromatin to MNase, DNase I and endogenous endonucleases was higher in male than female, and MNase as well as DNase I were more active in adult than old. Such sex- and age-dependent conformation of chromatin may attribute to differential expression of genes in the mouse brain.

Aging↗

Alterations in chromatin conformation are accompanied by reorganization of nonchromatin domains that contain U-snRNP protein p28 and nuclear protein p107.

The intranuclear distribution of nuclear matrix-associated protein p107 and the 28-kD Sm antigen of U-snRNPs have been studied using double-label immunofluorescence and immunoperoxidase electron microscopy. In interphase nuclei of HeLa cells, Novikoff hepatoma cells, and rat kangaroo kidney cells, p107 was confined to discrete interchromatin domains. The domains had an irregular contour, with an average diameter of 1-1.5 micron. Each domain appeared to be composed of interconnected granules. The Sm antigen colocalized and appeared concentrated in these domains but also showed some general nucleoplasmic distribution. During mitosis, the interchromatin domains disassembled such that the Sm portion redistributed to the perichromosomal and spindle regions and the p107 component redistributed throughout the mitotic cytoplasm. During anaphase, p107 assembled into discrete clusters throughout the mitotic cytoplasm. The Sm antigen was not a component of these clusters. Double-label immunofluorescence with anti-p107 and the anti-DNA tight-binding protein, AhNa1, showed that the extranuclear p107 domains assumed an interchromatin localization only after the chromosomes had decondensed. The correlation between chromosome decondensation and the occurrence of p107 within interchromatin domains was also observed during chicken erythrocyte nuclear reactivation. We propose that the discrete interchromatin domains that contain p107 and p28 may be important for processing and splicing of RNA and that their structural assembly within nuclei is sensitive to the presence of the transcriptionally active conformation of chromatin.

Animals↗

Parental chromosome-specific chromatin conformation in the imprinted U2af1-rs1 gene in the mouse.

The imprinted U2af1-rs1 gene on mouse chromosome 11 is expressed exclusively from the paternal allele. We found that U2af1-rs1 resides in a chromosomal domain that displays marked differences in chromatin conformation and DNA methylation between the parental chromosomes. Chromatin conformation was assayed in brain and liver, in fetuses, and in embryonic stem cells by sensitivity to nucleases in nuclei. In all these tissues, the unmethylated paternal chromosome is sensitive to DNase-I and MspI and has two DNase-I hypersensitive sites in the 5'-untranslated region. In brain and in differentiated stem cells, which display high levels of U2af1-rs1 expression, a paternal DNase-I hypersensitive site is also readily apparent in the promoter region. On the maternal chromosome, in contrast, the entire U2af1-rs1 gene and its promoter are highly resistant to DNase-I and MspI in all tissues analyzed and are fully methylated. No differential MNase sensitivity was detected in this imprinted domain. The parental chromosome-specific DNA methylation and chromatin conformation were also present in parthenogenetic and androgenetic cells and in tissues from animals maternally or paternally disomic for chromosome 11. This demonstrates that these parental chromosome-specific epigenotypes are independently established and maintained and provides no evidence for interallelic trans-sensing and counting mechanisms in U2af1-rs1.

Alleles↗

Promoter methylation inhibits APC gene expression by causing changes in chromatin conformation and interfering with the binding of transcription factor CCAAT-binding factor.

As an important regulator in Wnt-signaling pathway, the APC gene is involved in apoptosis and cell cycle arrest. The loss of APC function is observed in most familial adenomatous polyposis-associated and sporadic colorectal cancer. APC gene is frequently inactivated by DNA mutations. However, hypermethylation in APC gene promoter was also observed in different cancers. In this study, by analyzing the methylation status of APC promoter in 22 colorectal cancer cell lines with different APC expression levels, we identified Regions A and B in the promoter, where the methylation of CpG sites was invariably correlated with the loss of gene expression. By nuclease accessibility assay, we also observed a correlation between the closed chromatin conformation in APC promoter and loss of gene expression. When the nonexpressing cell lines were treated with a DNA methyltransferase inhibitor, 5-Aza-2'-Deoxycytidine, the APC expression in these cells was induced, CpG sites were demethylated, and closed chromatin conformation was opened. However, when these cell lines were treated with a histone deacetylase inhibitor, Trichostatin A, no significant changes in APC expression, methylation status, and chromatin conformation were observed. Using transient transfection assay, a CCAAT box located in Region B was identified, which was involved in up-regulation of APC expression. Methylation of CpG sites around the CCAAT box resulted in a significant inhibition in the gene expression. The specific binding of a transcription factor CCAAT-binding factor (CBF) to the CCAAT box was determined by electrophoretic mobility shift analysis. The binding was inhibited after CpG sites close to the CCAAT box were methylated, indicating that DNA methylation can silence gene expression through interfering with the binding of transcription factors to the promoter. The biological function of CBF in APC gene regulation was further indicated by the decrease of luciferase activities in cells cotransfected with a plasmid carrying APC promoter/luciferase gene and a plasmid expressing dominant negative CBF mutant. In summary, methylation of CpG sites around CCAAT box in APC promoter inhibits the gene expression by changing the chromatin conformation and interfering with the binding of transcription factor CBF to CCAAT box.

Adenomatous Polyposis Coli Protein↗

Changes in chromatin conformation regulate the 5-lipoxygenase gene expression during differentiation of HL60 cells.

The HL60 cell line does not express the 5-lipoxygenase gene prior to differentiation with various agents. In this paper we have shown by DNase I sensitivity that the chromatin conformation of the 5-lipoxygenase gene changes following differentiation of HL60 cells with dimethyl sulfoxide (DMSO). Moreover, run-on analysis suggests that transcription of the 5-lipoxygenase gene is enhanced after differentiation. We proposed that the chromatin conformation represses the expression of the 5-lipoxygenase gene in HL60 cell line and that differentiation of these cells with DMSO changes the chromatin conformation, which allows the expression of the 5-lipoxygenase gene. The HeLa cells which, like the HL60 cells, do not express the 5-lipoxygenase, were insensitive to DNase I treatment. These results suggest that chromatin structure might represent a form of regulation for the 5-lipoxygenase gene.

Arachidonate 5-Lipoxygenase↗

Structural basis of differential gene expression at eQTLs loci from high-resolution ensemble models of 3D single-cell chromatin conformations.

MOTIVATION: Techniques such as high-throughput chromosome conformation capture (Hi-C) have provided a wealth of information on nucleus organization and genome important for understanding gene expression regulation. Genome-Wide Association Studies have identified numerous loci associated with complex traits. Expression quantitative trait loci (eQTL) studies have further linked the genetic variants to alteration in expression levels of associated target genes across individuals. However, the functional roles of many eQTLs in noncoding regions remain unclear. Current joint analyses of Hi-C and eQTLs data lack advanced computational tools, limiting what can be learned from these data. RESULTS: We developed a computational method for simultaneous analysis of Hi-C and eQTL data, capable of identifying a small set of nonrandom interactions from all Hi-C interactions. Using these nonrandom interactions, we reconstructed large ensembles (&#xd7;105) of high-resolution single-cell 3D chromatin conformations with thorough sampling, accurately replicating Hi-C measurements. Our results revealed many-body interactions in chromatin conformation at the single-cell level within eQTL loci, providing a detailed view of how 3D chromatin structures form the physical foundation for gene regulation, including how genetic variants of eQTLs affect the expression of associated eGenes. Furthermore, our method can deconvolve chromatin heterogeneity and investigate the spatial associations of eQTLs and eGenes at subpopulation level, revealing their regulatory impacts on gene expression. Together, ensemble modeling of thoroughly sampled single-cell chromatin conformations combined with eQTL data, helps decipher how 3D chromatin structures provide the physical basis for gene regulation, expression control, and aid in understanding the overall structure-function relationships of genome organization. AVAILABILITY AND IMPLEMENTATION: It is available at https://github.com/uic-liang-lab/3DChromFolding-eQTL-Loci.

Quantitative Trait Loci↗

The active FMR1 promoter is associated with a large domain of altered chromatin conformation with embedded local histone modifications.

We have analyzed the effects of gene activation on chromatin conformation throughout an approximately 170-kb region comprising the human fragile X locus, which includes a single expressed gene, FMR1 (fragile X mental retardation 1). We have applied three approaches: (i) chromosome conformation capture, which assesses relative interaction frequencies of chromatin segments; (ii) an extension of this approach that identifies domains whose conformation differs from the average, which we developed and named chromosome conformation profiling; and (iii) ChIP analysis of histone modifications. We find that, in normal cells where FMR1 is active, the FMR1 promoter is at the center of a large ( approximately 50 kb) domain of reduced intersegment interactions. In contrast, in fragile X cells where FMR1 is inactive, chromatin conformation is uniform across the entire region. We also find that histone modifications that are characteristic of active genes occur tightly localized around the FMR1 promoter in normal cells and are absent in fragile X cells. Therefore, the expression-correlated change in conformation affects a significantly larger domain than that marked by histone modifications. Domain-wide changes in interaction probability could reflect increased chromatin expansion and may also be related to an altered spatial disposition that results in increased intermingling with unrelated loci. The described approaches are widely applicable to the study of conformational changes of any locus of interest.

Adult↗

Chromosomally derived sterile mice have a 'fertile' active XY chromatin conformation but no XY body.

We have previously shown that the sex chromosome bivalent of normal, fertile male mice possesses extensive regions of potentially active chromatin, even though, as has been shown by others, certain X-linked genes, and perhaps most of the X chromosome, become inactivated during pachytene. The male meiosis of a fertile (2;11) translocation carrier mouse, a chromosomally derived sterile (11; 19) translocation carrier and that of normal mice is compared. In situ nick translation shows a similar DNase I sensitivity pattern in the sex chromosomes of all examined mice. The X chromosome has four regions of potentially active chromatin conformation, two at the ends of the chromosome and two interstitial ones, coinciding with flexures which become prominent towards late pachytene. The Y chromosome is almost uniformly sensitive to DNase I. The similarity of chromatin conformation patterns in fertile and sterile mice is compatible with the hypothesis that unscheduled transcription of particular genes, possibly included in the active conformation regions, occurs in mice which become sterile. In the sterile (11;19) translocation carrier, a vast majority of all pachytenes are "associated": usually one unpaired segment of chromosome 19 is in end-to-end contact with the X chromosome. The tips of both unpaired segments of chromosome 19 have a thickened axis and display a peculiar chromatin appearance, similar to the modification of the centromeric tip of the X chromosome. Telomeric unpairedness of certain chromosome segments seems to be conducive to autosome-X chromosome association. We suggest that compartmentalization of the nucleus into an autosome mass and a fully developed, protruding, metabolically quiescent XY body, is a precondition for the normal progressing of meiosis. In the associated cells, the autosomal quadrivalent anchors the XY bivalent among the autosomes; as a consequence no XY body is formed. This interference with the course of compartmentalization leads to the abolishment of inactivation of part or all of the potentially active genes and results in meiotic arrest, and hence in sterility.

Animals↗

Chromatin conformation and salt-induced compaction: three-dimensional structural information from cryoelectron microscopy.

Cryoelectron microscopy has been used to examine the three-dimensional (3-D) conformation of small oligonucleosomes from chicken erythrocyte nuclei after vitrification in solutions of differing ionic strength. From tilt pairs of micrographs, the 3-D location and orientation of the nucleosomal disks, and the paths of segments of exposed linker can be obtained. In "low-salt" conditions (5 mM NaCl, 1 mM EDTA, pH 7.5), the average trinucleosome assumes the shape of an equilateral triangle, with nucleosomes at the vertices, and a length of exposed linker DNA between consecutive nucleosomes equivalent to approximately 46 bp. The two linker DNA segments converge at the central nucleosome. Removal of histones H1 and H5 results in a much more variable trinucleosome morphology, and the two linker DNA segments usually join the central nucleosome at different locations. Trinucleosomes vitrified in 20 mM NaCl, 1 mM EDTA, (the salt concentration producing the maximal increase in sedimentation), reveal that compaction occurs by a reduction in the included angle made by the linker DNA segments at the central nucleosome, and does not involve a reduction in the distance between consecutive nucleosomes. Frequently, there is also a change in morphology at the linker entry-exit site. At 40 mM NaCl, there is no further change in trinucleosome morphology, but polynucleosomes are appreciably more compact. Nevertheless, the 3-D zig-zag conformation observed in polynucleosomes at low salt is retained at 40 mM NaCl, and individual nucleosome disks remain separated from each other. There is no evidence for the formation of solenoidal arrangements within polynucleosomes. Comparison of the solution conformation of individual oligonucleosomes with data from physical measurements on bulk chromatin samples suggests that the latter should be reinterpreted. The new data support the concept of an irregular zig-zag chromatin conformation in solution over a range of ionic strengths, in agreement with other in situ (McDowall, A.W., J.M. Smith, and J. Dubochet. 1986, EMBO (Eur. Mol. Biol. Organ.) J.5: 1395-1402; Horowitz, R.A., D.A. Agard, J.W. Sedat, and C.L. Woodcock, 1994. J. Cell Biol. 125:1-10), and in vitro conclusions (van Holde, K., and J. Zlatanova. 1995. J. Biol. Chem. 270:8373-8376). Cryoelectron microscopy also provides a way to determine the 3-D conformation of naturally occurring chromatins in which precise nucleosome positioning plays a role in transcriptional regulation.

Animals↗

[Changes in chromatin conformation induced by ionizing radiations with different LETs in resting and proliferating hepatocytes from rats of different ages].

The method of flow cytometry was used to study conformation changes in rat hepatocyte chromatin exposed to various doses of X-rays and fission neutrons (mean energy of 0.85 MeV). Chromatin decondensation induces by both X-rays and neutrons was shown to be a function of dose. The saturation effect was observed for X-rays doses ranging from 4 to 6 Gy; for fission neutrons no saturation effect was noted within the dose range from 0.5 to 4 Gy. The initial chromatin level, that changed during the cell cycle and upon ageing, influence induction of conformation changes in the chromatin. The authors discuss the dependence of the processes of repair and fixation of damages to hereditary cell structure on the chromatin conformation at the time of exposure.

Aging↗

Examination of DNA sequences undergoing chromatin conformation changes at a variegating breakpoint in Drosophila melanogaster.

Position effect variegation in Drosophila melanogaster is associated with the inability of certain genes to be correctly expressed in a proportion of cells, giving a mosaic phenotype. The lack of expression is thought to be due to alterations in the gene's chromatin structure due to its proximity to a region of heterochromatin. Because of the difficulties involved, there is little biochemical data to support the intuitively appealing model of 'heterochromatin spreading' used to explain this phenomenon. Differences in restriction fragment length were used to distinguish DNA regions from either normal (non-position affected) or rearranged (position affected) chromosomes so as to examine possible changes in gene copy number and the effects of endogenous nucleases. DNA sequences at the breakpoint of In(1)wm4, which variegates for the white gene, were assayed under conditions where the chromatin conformation was altered using second site modifier mutations (Su(var) or En(var)). No change in the DNA sequence copy number was observed at either chromosome breakpoint, relative to wild type, when either suppressor or enhancer mutations were present. Therefore copy number change, through differential polyploidization or somatic gene loss, is not affected by Su(var) or En(var) induced changes in the chromatin conformation. Initial experiments showed a gross difference in the sensitivity of DNA to endogenous nucleases that appeared associated with Su(var) and En(var) mutations. En(var) mutation bearing samples appeared delayed in the digestion, relative to Su(var).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

High sensitivity of chromatin conformational state of human leukocytes to low-dose X-rays.

Changes in the chromatin conformational state (CCS) of human leukocytes were detected by the anomalous viscosity time dependence (AVTD) method. The dose dependence was studied for seven donors with doses of up to 10 cGy. X-rays caused no statistically significant changes in the leukocytes of two of the donors. The dose dependences registered on leukocytes of the other donors showed some distinctions which may be due to individual traits of the donors. Extrapolation of all the results produced a nonlinear dose dependence which consisted of two sections. The first one was characterized by a fast growth of the effect, the second section was extrapolated to a slightly sloping linear dependence which was close to a plateau. It was shown that the AVTD method was highly sensitive to X-rays and can register changes in the CCS of leukocytes exposed to doses of about 0.5 cGy. The possible role of DNA breaks and processes of ionization and excitation are analyzed.

Adult↗