15 research outputs found
Rivalutazione della OPT nell'indagine diagnostica preliminare delle disfunzioni cervico-cranio-mandibolari
No full textResponse of human cord blood cells to styrene exposure: evaluation of its effects on apoptosis and gene expression by genomic technology
No full textStyrene is one of the most important monomers produced worldwide, and it finds major use in the production of polystyrene, acrylonitrile-butadiene- styrene resins and unsaturated polystyrene resins. Epidemiological studies on styrene showed that the malignancies observed most frequently in humans after exposure are related to the lymphatic and haemopoietic system. IARC classified styrene a possible carcinogenic to humans (Group 2B). In this study, we evaluated the effect of styrene on gene expression profiles of human cord blood cells, as well as its activity on the apoptosis and bcl-2 related protein expression. Data demonstrated that, after 24 and 48 h of exposure, styrene (800 μM) induced an increase in the necrosis of mononuclear cord blood cells, whereas it did not cause any increase in the apoptotic process. Western blot analysis revealed a modified expression of Bax, BCl-2, c-Jun, c-Fos and Raf-1 proteins in the human cord blood cells after direct exposure to styrene, whereas p53 expression did not change. Furthermore, Macroarray analysis showed that styrene changed cord blood gene expression, inducing up-regulation of monocyte chemotactic protein 1 (MCP-1), and down-regulation of CC chemokine receptor type 1 (CCR-1) and SLP-76 tyrosine-phosphoprotein
Pancreas developing markers expressed on human mononucleated umbilical cord blood cells
No full textHaematopoietic system represents the main source of haematopoietic stem cells and probably of multipotential adult progenitor cells and mesenchimal stem cells at first described as colony forming unit-fibroblast. Whereas there are many studies on the gene expression profile of the different precursors along their haematopoietic differentiation, few data (sometimes conflicting) have been reported about the phenotype of the cells (present in bone marrow and possibly in cord blood) able to differentiate into non-haematopoietic cells. As both postnatal bone marrow and umbilical cord blood contain nestin positive cells able to proliferate and differentiate into the main neural phenotype (neuron, astroglia and oligodendroglia) many authors considered nestin a neuroepithelial precursor marker that seems to be essential also in multipotential progenitor cells of pancreas present both in rat and in human pancreatic islets (called nestin positive islet derived progenitors). Although the importance of nestin in these cells appears to be evident, it remains yet to clarify the number and the sequential expression of the genes coding all the transcription factors essential for beta cells differentiation and therefore the conditions able to induce the expression of many important transcription factors genes such as isl-1, pax-4, pdx-1 and ngn-3. Among them pdx-1 is a gene essential for pancreas development which is able to control ngn-3 in activating the expression of other differentiation factors for endocrine cells. Here, we describe for the first time in human umbilical cord blood cells (UCB) the pattern of expression of a panel of markers (nestin, CK-8, CK-18) and transcription factors (Isl-1, Pdx-1, Pax-4, Ngn-3) considered important for beta cells differentiation. Our data demonstrate that UCB contains a cell population having a phenotype very similar to endocrine cell precursors in transition to beta cells
Naphthalene exposure: Effects on gene expression and proliferation in human cord blood cells
No full textIn this study, the effect of naphthalene on the induction of apoptosis and gene expression profiles in cord blood cells has been evaluated, as well as its activity on the BCL-2 related protein expression. After 6, 24, and 48 h of exposure to naphthalene (500 μM , a decrease in cell death was observed: the cells became more resistant to the toxicant and capable of surviving after the treatment. A Western blot analysis revealed an overexpression of BCL-2, c-JUN, c-FOS, and RAF-1 proteins, which are involved in the antiapoptotic response and in the regulation of cell growth, differentiation, and development. Furthermore, macroarray analysis showed that naphthalene modified cord blood gene expression, inducing IL-8 precursor and T-cell transcription factor and decreasing the level of RNA-binding protein FUS/TLS
Gene and Protein Expressions in Human Cord Blood Cells After Exposure to Acrylonitrile
No full textAcrylonitrile is a very high volume industrial
chemical used primarily in the manufacture
of plastics and rubber, which displays a pronounced
acute toxicity and may be carcinogenic. The damage
to the hematopoietic function by acrylonitrile may result
from interference with cytokine production and
cytokine receptor binding. Our present data show that
acrylonitrile modulates the expression of some genes
implicated in cell differentiation, cell-cycle progression,
and clonogenic potential of human cord blood
cells.Amacroarray hybridization analysis showed that
expression of the CXCR4, MCP-1, and MRP8 genes was
modified by acrylonitrile exposure. Moreover, the acrylonitrile
cell target seems to be the myeloid compartment,
as assessed by a CFU-GM assay. In particular,
the downregulation of CXCR4, MCP1, and MRP8 can
be responsible for the observed reduction of cell proliferation
and clonogenic capability of CFU-GM precursors.
A Western blot assay showed an acrylonitriledependent
induction of Bax, while Bcl-2 expression
changed only after 48 h of chemical exposure. Bax
was overexpressed in respect to Bcl-2, and this fact
can be responsible for the induction in cell death after
24 h of treatment. C-fos and c-jun were also downregulated
after 24 h and 6 h of treatment, respectively.JRC.I.2 - Validation of biomedical testing method
Clonogenicity and gene expression modulation in the bone marrow of mice chronically exposed to arsenic and atrazine.
No full textThe clonogenicity of myeloid progenitors (CFU-GM) and the modulation of gene expression of 1185 cancer-related genes by DNA-macroarrays in bone marrow were used to investigate in male and female mice the combined effects of continuous exposure to arsenate and atrazine in drinking water.
In male mice, the exposure to arsenate or to atrazine alone and the combined exposure did not change the clonogenicity of the progenitors. In females the percentage of CFU-GM decreased significantly after atrazine exposure, did not change with arsenic treatment, but dramatically increased after the combined exposure to the two chemicals.
Results from microarrays indicate that atrazine alone didn’t stimulate the expression of any of the cancer genes analyzed in both male and female. Arsenic induced gene expression modulation only in female and had no effects on male. Major significant changes on the gene expression in bone marrow cells resulted following the co-exposure to arsenic and atrazine in both male and female.
These results indicate that co-exposure of mice to atrazine and arsenate induces significant effects at the level of transcriptional activation of genes in bone marrow cells, as well as stimulating the myeloid progenitors to proliferate, particularly when co-administered in drinking water to female mice
Combined in-utero and juvenile exposure of mice to arsenate and atrazine in drinking water modulates the gene expression and clonogenicity of myeloid progenitors in bone marrow.
No full textIncreasing evidence proves that human fetuses are exposed to multiple risk factors and major concerns have been expressed towards exposure to potential endocrine modulating chemicals at early stage of life and during growth. Understanding that exposures occur as mixture of chemicals and that they converge on other inherent and environmental risk-modulating factors, there is a need to develop experimental models to assess the effects of exposure to multiple chemicals during different stage of life.
In the present study, the clonogenicity of myeloid progenitors (CFU-GM) and the modulation of gene expression of 1197 cancer-related genes (DNA macroarrays) in bone marrow were used to investigate in male and female young mice the combined effects of continuous exposure to arsenate and atrazine in drinking water.
Female adult mice were treated with arsenate in drinking water (1 mg As/L) for 10 days before mating and during the gestation.
Offspring were randomly put into separate groups of males and females. One group of arsenic exposed offspring were exposed for 4 months to atrazine (1mg Atr/L) and arsenate (1 mg As/L) in drinking water (As+Atr). One group of each of arsenic unexposed offspring were exposed for 4 months to atrazine (1mg Atr/L) in drinking water (Atr). Additional arsenate (1 mg As/L) was given to one group of arsenic exposed offspring (As). Control mice without any treatment were also analysed (Ctrl).
In male mice the exposure to arsenate or to atrazine alone did not result in significant changes on the gene expression in bone marrow cells, whereas, co-exposure to arsenic and atrazine (As+Atr) resulted in a significant up-modulation of gene expression. The percentage of CFU-GM weakly decreased after exposure to individual compounds, while the co-exposure did not change the clonogenicity of the progenitors.
In female mice, the co-exposure to both chemicals resulted in a drastic up-modulation of gene expression, while in these cells the single treatments showed a up-modulation of few genes as well. The percentage of CFU-GM decreased significantly after atrazine exposure, did not change with arsenic treatment, but dramatically increased after the combined administration.
These results indicate that in-utero and juvenile co-exposure of mice to atrazine and arsenate induce significant effects at the level of transcriptional activation of genes in bone marrow cells, as well as stimulating the myeloid progenitors to proliferate, particularly when co-administered in drinking water to female mice
Metabolite fingerprinting of raw propolis from different Italian regions by innovative HPLC-ESI-MS and GC-MS
No full textThis study was aimed at a detailed chromatographic analysis of propolis samples by means of the development and application of innovative HPLC-ESI-MS and HS-SPME-GC-MS techniques to provide a complete fingerprinting of the biologically active components
Isolation and characterization of cancer preventive polyphenolic compounds from a Terminalia chebula Retzius extract
No full textIn this study, a bioassay-guided fractionation was carried out from a Terminalia chebula Retzius extract to isolate and characterize the polyphenolic compounds that were tested for their cancer preventive activities
Sensitivity of human Cord Blood Cells to Tetrachloroethylene: Cellular and Molecular Endpoints
No full textThe International Agency for Research on
Cancer (IARC) currently lists tetrachloroethylene [perchloroethylene
(PCE)] as being carcinogenic in animals.
PCE is listed as possibly carcinogenic to humans
upon occupational exposure. Human exposure to PCE
can produce oesophageal cancer, cervical cancer, non-
Hodgkin’s lymphoma, urinary bladder cancer and leukemia.
This work shows that PCE modulates the
expression of some genes implicated in cancer induction,
cell differentiation, cell-cycle progression, and the survival
and clonogenic potential of human cord blood
cells. After exposure to the compound, the modulated
genes were involved in inflammatory responses as with
the mitogen-activated protein kinase 14 (MPK 14), or in
tumor and metastasis progression as with the matrix
metalloproteinase 17 (MMP 17), in cell proliferation as
with c-jun and c-fos, and moreover in the apoptotic
process as with interferon alpha-inducible protein (IFI),
BAX and BCL-2. Analysis of cord blood cells via flow
cytometry showed that PCE treatment induced a statistically
significant increase in necrosis after 24 h, while
the clonogenicity of Human Colony-Forming Unit-
Granulocyte/Macrophage (CFU-GM) and Burst-
Forming Unit-Erythrocyte (BFU-E) progenitors did not
change. In conclusion, our data showed that PCE affected
various pathways involved in cancer induction,
but its action on cell proliferation and differentiation is
not yet clearly understood.JRC.I.2 - Validation of biomedical testing method
