Arsenic-induced DNA hypomethylation affects chromosomal instability in mammalian cells

Early genetic instability induced in dividing V79-Cl3 Chinese hamster cells by inorganic arsenic, as demonstrated in our previous investigation, was evidenced by aneuploidy and nuclear abnormalities, but not by chromosomal rearrangements. Here we report the results of cytogenetic and morphological analyses performed on the progeny of cells dividing at the end of sodium arsenite treatment after they had been expanded through 120 generations (ASO cells) and then cloned. The acquired genetic instability persisted and was increased by highly unstable chromosomal rearrangements, namely dicentric chromosomes and telomeric associations, which were not seen following acute exposure. A peculiar finding was the preferential involvement of a particular chromosome in dicentric rearrangements observed in some isolated ASO clones. Interestingly, by immunostaining with anti-5-methylcytosine antibodies the genome-wide DNA hypomethylation, induced by arsenic immediately after the acute treatment, was found to affect those ASO clones characterized by aneuploidy and chromosomal rearrangements. These findings demonstrate that short-term exposure to arsenic has long-term effects and suggest that genome-wide DNA hypomethylation enhances genetic instability

Spontaneous Endoreduplication, Tetraploidy and Chromosome Breakage in Lymphocyte Cultures from Healthy Subjects

SUMMARY42,703 metaphases of peripheral lymphocytes from 20 healthy subjects (10 women and 10 men) were examined in order to establish the frequency of endoreduplicated cells and of tetraploid cells without diplochromosomes. Frequencies were found to be 0.016% and 0.112%, respectively. The two sexes did not differ as to the frequency of tetraploid cells, with and without diplochromosomes (about 0.13% in either sex). In a total of 2,135 well spread metaphases examined, 26 cells (i.e. 1.2%) with chromosomal breaks were found. Again, no significant differences between the two sexes were found as to such chromosome abnormalities

Persistent dysregulation of DNA methylation in cells with arsenic-induced genomic instability

The mechanisms by which arsenic-induced genomic instability is initiated and maintained are poorly understood. In previous studies long-term progression of chromosomal instability was typified by increasing aneuploidy in Chinese hamster V79 and human keratinocyte cells treated with arsenite for a 24 hr exposure period followed by growth in arsenic-free medium for 40-120 cell generations. In the current study the role of progressive DNA methylation changes was evaluated in long-term cell cultures after brief arsenite treatments as above. We have found altered genomic methylation patterns in cells that were briefly exposed to arsenic with evidence for widespread dysregulation of CpG methylation that persists for many population doublings after the treatment. In V79 cell populations, progressive aneuploidy increases were notable by 50 cell generations after a 24 hr exposure to 1-10 uM arsenite. Dicentric chromosomes and/or telomeric associations, as well as complex chromosome rearrangements, occurred by 90 cells generations post treatment; and mutator and transformed phenotypes began to appear thereafter. This increasing genomic instability correlated with modifications of global DNA methylation patterns in V79 cells evaluated by 5-methylcytosine antibody binding and MeSAP-PCR. The results show that short-term exposure to arsenite induced an apparent genome hypomethylating effect within a short time after exposure. In identical protocols using human HaCaT keratinocytes exposed to low doses of arsenite (0.05-0.1 M) for 24 hr, genomewide methylation levels were measured by LINE1 pyrosequencing and gene-specific methylation status was assessed by Methylation-Specific-PCR for up to 40 generations post exposure. Global demethylation following treatment was supported by preliminary LINE-1 studies. Moreover, the study of gene-specific MSP and determination of expression levels by RT-PCR of several genes (p16, hMLH1, hMSH2, DNMT1, DNMT3a and DNMT3b) demonstrated that hMSH2 gene was epigenetically regulated by arsenite and that down regulation of DNMT3a and DNMT3b genes occurred in an arsenite dose-dependent manner. The results reported here demonstrate that acute 24 hr arsenic exposure promptly induces genome wide DNA hypomethylation, and support the hypothesis that the cells continue to undergo epigenetic reprogramming both at the gene and genomic levels in the absence of further arsenite treatment; thus likely contributing to long-lasting genomic instability that manifests as aberrant chromosomal, mutator and cell transformation effects

Structural modifications induced in ZIF-8 by interaction with Cu2+ions in water remediation applications

Metal-organic frameworks (MOF) are very promising materials, as they exhibit many exciting properties inspiring many outstanding applications. One very intriguing property of a class of MOF consists in their ability to breath, i.e. to undergo a crystalline to-crystalline structural change, usually induced by modifying the temperature, applying external pressure or by adsorbing of specific gases [1]. Such structural changes in turn affect many properties of the material, further increasing the potential applications of these materials. The advantages of the breathing process in sensing applications, for example, are obvious. One of the most interesting breathing MOF is MIL-53(Al) [2]. It has strong potentialities in many fields, as adsorption, separation and storage of gases, catalysis, drug delivery, sensing [3,4]. Since its first report, MIL-53(Al) has gained the role of prototype system, giving the opportunity to unveil many properties pertaining to such outstanding class of highly reactive (breathing) MOF...

Investigation on the luminescence properties of bare and Rhodamine B functionalized Zr-MOF-808

Metal organic frameworks (MOFs) are materials well known for their high surface and catalytic properties as well as because they are relatively easy to synthesize and, in some cases, extremely f lexible.[1] Recently, there has been also a growing interest in the optical properties of these materials, particularly in luminescence, which has potential applications in various fields, such as sensors, LEDs, scintillators, and bioimaging agents....

Origin of the solid-state luminescence of MIL-53(Al) and its connection to the local crystalline structure

Metal-organic frameworks (MOFs) are extensively studied due to their unique surface properties, enabling many intriguing applications. Breathing MOFs, a subclass of MOFs, have gained recent interest for their ability to undergo structural changes based on factors like temperature, pressure, adsorbed molecules. Certain MOFs also exhibit remarkable optical properties useful for applications such as sensors, light-emitting diodes, and scintillators. The most promising MOFs possess high porosity, breathing properties, and photoluminescence activities, allowing for improved device responsiveness and selectivity. Understanding the relationship between crystal structures and photoluminescence properties is crucial in these cases. As studies on this topic are still very limited, we report for the first time an exhaustive study on the solid-state luminescence of the breathing MOF MIL-53(Al), that can stabilize in three different crystalline structures: open-pore, hydrated narrow-pore and closed-pore. We unveil a fascinating solid-state luminescence spectrum, comprising three partially overlapping bands, and elucidate the intricate electronic transitions within each band as well as their intimate correlation with the local crystalline structures. Our characterizations of spectroscopic properties and decay times provide a deeper understanding of the luminescent behaviour of MIL-53(Al) and demonstrate that is possible to identify present crystalline structures by optical measurements or to modify the optical properties inducing structural transitions for this type of materials. These insights could help to design next-generation, selective sensors or smart light emitting devices

Sister chromatid exchange in Waldenström's macroglobulinemia

Results on sister chromatid exchange (SCE) frequency and interchromosomal distribution in bone marrow and peripheral blood cultures from patients with Waldenström's macroglobulinemia are reported. PHA-stimulated bone marrow cultures showed increased SCE frequencies in all 12 patients examined. The increase was particularly high in two cases (17.07 and 16.77 SCE/cell, respectively) and, in one of them, a very high SCE level was found in PHA-stimulated peripheral blood culture (40.81 SCE/cell). In LPS-stimulated cultures, increased SCE levels were observed in some patients. Comparison between SCE frequency in bone marrow cell cultures with either mitogen showed a significant increase in PHA-stimulated cultures. Analysis of the interchromosomal SCE distribution revealed significant differences with respect to the control values; however, these differences were variable in the different patients. In pooled data of PHA-stimulated bone marrow cultures, there were differences between expected and observed SCEs in chromosomes 1 and 2 and in B, E, F, and G chromosome groups. Results of cell cycle modifications are also reported. © 1993

Possible involvement of the IL4 gene in Waldenström's macroglobulinemia

We report the results of a molecular investigation of 11 patients affected by Waldenström's macroglobulinemia, a rare B-cell malignancy characterized by an excessive proliferation of immunoglobulin(Ig)M-secreting plasmacytoid cells. In particular, we studied the interleukin-4 (IL4) gene, which codes for a B-specific growth factor capable of stimulating the proliferation and differentiation of secreting plasma cells. By Southern hybridization, in three patients we found the presence of additional bands in comparison with the expected pattern; moreover, these bands showed a different degree of intensity. © 1994