scholarly journals Dose response relationships for gamma radiation induced chromosomal instability

2017 ◽  
Author(s):  
Y.A. Eidelman ◽  
S.V. Slanina ◽  
V.S. Pyatenko ◽  
I.K. Khvostunov ◽  
S.G. Andreev
Keyword(s):  
Gamma Radiation ◽  
Cell Lines ◽  
Dose Response ◽  
Chromosomal Instability ◽  
Response Curve ◽  
Mechanistic Modeling ◽  
Published Data ◽  
Dependent Behavior ◽  
Radiation Induced ◽  
Dose Dependent

ABSTRACTDifferent cell lines demonstrate various dose response for radiation-induced chromosomal instability (RICI). To clarify the origin of differences we analyzed own and published data on RICI for four cell lines, V79, TK6, WTK1 and CHO-K1 on the basis of the mechanistic RICI model. We conclude that observable dose-response shapes, both plateau-like and strong dose dependent behavior, may be jointly explained by the same model of RICI. Mechanistic modeling reveals that a variation of certain set of RICI parameters leads to strong modification of dose-response curve.

scholarly journals Quantitative relationships for radiation induced chromosome instability: data analysis

2017 ◽  
Author(s):  
Y.A. Eidelman ◽  
S.V. Slanina ◽  
V.S. Pyatenko ◽  
I.K. Khvostunov ◽  
S.G. Andreev
Keyword(s):  
Data Analysis ◽  
Cell Line ◽  
Cell Lines ◽  
Chromosomal Instability ◽  
Chromosome Instability ◽  
Published Data ◽  
Proposed Model ◽  
Radiation Induced

ABSTRACTThe experimental observations demonstrate that different cell lines reveal various shape of dynamic curves for radiation-induced chromosomal instability (RICI). We analyzed our own and published data on RICI for three cell lines, CHO-K1, V79 and TK6, on the basis of the mechanistic RICI model. We demonstrate that all three dynamic curves can be successfully described by the proposed model with partially cell line specific parameters.

The Dose Response Curve for Radiation-Induced Life Shortening

1969 ◽  
Vol 24 (4) ◽  
pp. 451-456 ◽  
Author(s):  
J. M. Yuhas
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Radiation Induced

On the Shape of the Dose-response Curve for HeLa Cells cultured in vitro and exposed to Gamma-radiation

Nature ◽  
1966 ◽  
Vol 209 (5030) ◽  
pp. 1363-1364 ◽  
Author(s):  
JOEL S. BEDFORD ◽  
ERIC J. HALL
Keyword(s):  
Gamma Radiation ◽  
Dose Response ◽  
Hela Cells ◽  
Response Curve ◽  
Dose Response Curve ◽  
Cells Cultured

Modeling study of dose-response relationships for radiation-induced chromosomal instability

2013 ◽  
Vol 451 (1) ◽  
pp. 171-175 ◽  
Author(s):  
S. G. Andreev ◽  
Ya. A. Eidelman ◽  
I. V. Salnikov ◽  
S. V. Slanina
Keyword(s):  
Dose Response ◽  
Chromosomal Instability ◽  
Radiation Induced ◽  
Modeling Study

scholarly journals Distinct vascular genomic response of proton and gamma radiation

2018 ◽  
Author(s):  
Ricciotti Emanuela ◽  
Dimitra Sarantopoulou ◽  
Gregory R. Grant ◽  
Jenine K. Sanzari ◽  
Gabriel S. Krigsfeld ◽  
...  
Keyword(s):  
Gamma Radiation ◽  
Dose Response ◽  
Photon Radiation ◽  
Radiation Response ◽  
Whole Body ◽  
Proton Radiation ◽  
Vascular Effects ◽  
Radiation Induced ◽  
Total Body ◽  
Genomic Response

AbstractPurpose. The cardiovascular biology of proton radiotherapy is not well understood. We aimed to compare the genomic dose-response to proton and gamma radiation of the mouse aorta to assess whether their vascular effects may diverge.Materials and methods.We performed comparative RNA sequencing of the aorta following (4 hrs) total-body proton and gamma irradiation (0.5 - 200 cGy whole body dose, 10 dose levels) of conscious mice. A trend analysis identified genes that showed a dose response.Results.While fewer genes were dose-responsive to proton than gamma radiation (29 vs. 194 genes;q-value ≤ 0.1), the magnitude of the effect was greater. Highly responsive genes were enriched for radiation response pathways (DNA damage, apoptosis, cellular stress and inflammation;p-value ≤ 0.01). Gamma, but not proton radiation induced additionally genes in vasculature specific pathways. Genes responsive to both radiation types showed almost perfectly superimposable dose-response relationships.Conclusions.Despite the activation of canonical radiation response pathways by both radiation types, we detected marked differences in the genomic response of the murine aorta. Models of cardiovascular risk based on photon radiation may not accurately predict the risk associated with proton radiation.

scholarly journals Radiation-induced effects in PC-3 and DU-145 human prostate cancer cells

2003 ◽  
Vol 11 (3) ◽  
pp. 197-197
Author(s):  
Vesna Vucic ◽  
Ana Niciforovic ◽  
Miroslav Adzic ◽  
Nevena Tisma ◽  
Dragana Jankovic ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cell Lines ◽  
Trypan Blue ◽  
Prostate Cancer Cell ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Human Prostate Cancer Cell ◽  
Radiation Induced ◽  
Dose Dependent

Background: Prostate cancer is the first as an incidence and the second as a cause of the oncologic mortality in the male population. There is a broad range of possibilities in the prostate cancer therapy. However, there is also much controversy on the most appropriate treatment in the various stages of the disease. Advanced disease is mostly treated by radiation therapy, sometimes in combination with hormone or chemotherapy. Irradiation induces damage of cell biomolecules, which can lead to the arrest in cell division, or to apoptotic or necrotic cell death. The aim of this study was to determine the dose dependence of radiation-induced cell death in two human prostate cancer cell lines, and to define the form of death of these cells. Methods: Human prostate cancer cell lines PC-3 and DU-145 were irradiated with 2 - 30 Gy from 60 Co g-source, at the dose rate of 20 Gy/h. The effect of irradiation on cell viability, morphology and DNA structure were followed 24 - 72 hours after treatment. Cells were analyzed by trypan blue exclusion assay, flow cytometry and DNA gel electrophoresis. Simultaneous staining of cells with Annexin V-FITC and propidium iodide enabled distinction of early apoptosis from late apoptosis and/or necrosis. Results: The results of trypan blue staining indicated that radiation-induced cell death was both time and dose dependent process. According to flow-cytometry and DNA fragmentation assay, necrosis was the prevailing form of the radiation-induced cell death in both PC-3 and DU-145 cells. The apoptosis occurred in insignificant number of cells, probably due to the mutant p53 gene present in both cell lines. The cell necrosis was dose dependent and was most pronounced 72 hours post treatment. Conclusion The prevailing form of radiation-induced PC-3 and DU-145 cell death is necrosis. Both PC-3 and DU-145 are rather radioresistant cell lines, as the dose necessary to induce 50% decrease in viable cell number is about 10 Gy.

scholarly journals An Evaluation of Boar Spermatozoa as a Biosensor for the Detection of Sublethal and Lethal Toxicity

Toxins ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 463 ◽  
Author(s):  
Emmanuelle Castagnoli ◽  
Johanna Salo ◽  
Matti Toivonen ◽  
Tamás Marik ◽  
Raimo Mikkola ◽  
...  
Keyword(s):  
Somatic Cell ◽  
Cell Lines ◽  
Dose Response ◽  
Response Curve ◽  
Membrane Integrity ◽  
Dose Response Curve ◽  
Motility Index ◽  
Lethal Toxicity ◽  
Boar Spermatozoa ◽  
Motility Inhibition

A novel, objective, and rapid computed motility inhibition (CMI) assay was developed to identify and assess sublethal injury in toxin-exposed boar spermatozoa and compared with a subjective visual motility inhibition (VMI) assay. The CMI values were calculated from digital micrographic videos using a custom MATLAB® script by contrasting the motility index values of each experiment with those of the background and control experiments. Following a comparison of the CMI and VMI assays results, it was determined that their agreement depended on the shape of the dose-response curve. Toxins that exhibited a steep slope were indicative of good agreement between the assays. Those depicted by a gentle decline in the slope of the dose-response curve, the CMI assay were shown to be two times more sensitive than the VMI assay. The CMI assay was highly sensitive to the inhibition of mitochondrial function and glucose transport activity by sublethal doses of toxins and to disruption of cellular cation homeostasis by carrier ionophoric toxins, when compared to the cytotoxicity and lethal toxicity assays (i.e., that evaluated the inhibition of cell proliferation in somatic cell lines (FL, PK-15, and MNA cells)) and disruption to spermatozoa membrane integrity. The CMI assay recognized subtle sublethal toxicity changes in metabolism, manifested as a decrease in boar spermatozoa motility. Thus, it was feasible to effectively compare the objectively-measured numerical values for motility inhibition using the CMI assay against those reflecting lethal damage in the spermatozoa cells and somatic cell lines using a cytotoxicity assay.

scholarly journals Differential proliferative responses of cultured Schwann cells to axolemma- and myelin-enriched fractions. I. Biochemical studies.

1984 ◽  
Vol 99 (6) ◽  
pp. 2309-2313 ◽  
Author(s):  
J E Yoshino ◽  
M P Dinneen ◽  
B L Lewis ◽  
J H Meador-Woodruff ◽  
G H Devries
Keyword(s):  
Schwann Cells ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Hill Coefficient ◽  
Maximal Response ◽  
Response Curves ◽  
Cultured Schwann Cells ◽  
Rat Brainstem ◽  
Dose Dependent

Cultured rat Schwann cells were treated for 72 h with axolemma- and myelin-enriched fractions prepared from rat brainstem. [3H]Thymidine was added to the cultures 48 h before the termination of the experiment. Although, both fractions produced a dose-dependent uptake of label into Schwann cells, the shape of the dose response curves and rates at which [3H]thymidine was incorporated were different. The axolemma-enriched fraction produced a sigmoid dose response curve with a Hill coefficient of 2.05. The dose response curve for myelin rose sharply and saturated at a level that was approximately 50% of the maximal response observed with axolemma. Schwann cells that had been treated with axolemma exhibited little change in the rate of [3H]thymidine incorporation from 36-72 h after the addition of the membranes. In contrast, Schwann cells accumulated label three times faster during the 48-72-h period following the addition of myelin to the cultures when compared with the rate during the preceding 12-h interval. Furthermore, the mitogenic activity of the myelin-enriched fraction was decreased by the addition of ammonium chloride, a lysosomal inhibitor, whereas the activity of the axolemmal fraction was not impaired.

scholarly journals Novel Histone Deacetilase (HDAC) Inhibitors: In Vitro Effects on Leukemic Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4946-4946
Author(s):  
Maria Rosaria Ricciardi ◽  
Roberto Licchetta ◽  
Paola Bergamo ◽  
Stefano Iacovelli ◽  
Andrea Miele ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cell Line ◽  
Cell Lines ◽  
Mtt Assay ◽  
Dose Response ◽  
Lymphoid Cell ◽  
Myeloid Leukemia ◽  
Response Curve ◽  
Myeloid Cell ◽  
Lymphoid Cell Line

Abstract Abstract 4946 Histone deacetylase inhibitors (HDAC-I) are a class of agents with the capacity to induce acetylation of histone and non-histone proteins. These molecules have been intensively investigated in a variety of malignancies because of their ability to inhibit proliferation, induce differentiation and apoptosis in tumor cells. However, clinical response to clinically available HDAC-I have been obtained only in a proportion of patients, prompting further studies aimed at identifying more active compounds and at defining the molecular mechanisms of response to this class of agents. Acetyl-L-carnitine (ALCAR) is a metabolic intermediate that facilitates the influx and efflux of acetyl groups across the mitochondrial inner membrane, thereby contributing to the regulation of energy production and metabolism. ALCAR activity as a modulator of cellular stress response has prompted its use to protect against chemotherapy-induced neurotoxicity. However, ALCAR effects on neoplastic cells are still not defined, especially in combination with chemotherapy. Here we investigated the effects of MS-275, a HDAC-I, on cell proliferation and apoptosis in cell line models of acute myeloid leukemia (AML) acute lymphoblastic leukemia (ALL), and multiple myeloma (MM), in comparison with vorinostat also known as SAHA (suberoyl anilid hydroxamic acid), the most widely used HDAC-I in clinical setting. HDAC-I were tested at doses ranging from 5 to 5000nM. In addition, the effects of simultaneous exposure to 10 mM of ALCAR and selected sub-toxic concentration of HDAC-I were analyzed. The cytotoxic effect of the treatment was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The drug concentration inducing 50 % cell killing (IC-50) was calculated from the dose-response curve. Cell cycle inhibition and induction of apoptosis were analyzed by flow cytometry using the Acridine- Orange (AO) technique. Results indicated that the tested compound MS-275 significantly inhibited cell growth, as assessed by MTT assay, when used at of 5000nM. Comparative analysis of the efficacy of the two different HDAC-I compounds indicated that MS-275 was the more effective agent and the only one with clear dose-dependent activity, while SAHA displayed a flat dose-response curve, which dropped only at the highest concentration. In particular, the myeloid cell line Molm-13 was strikingly sensitive to MS-275 (IC50: < 15 nM), U937 and HL60 myeloid cell lines, the lymphoid cell line Jurkat and the MM cell line ARH-77 showed intermediate sensitivity (IC50: < 1000 nM), while the lymphoid cell line CEM R was resistant (IC50 > 10 uM). SAHA showed no activity in U937 cells when used at concentrations ranging from 100 to 1000 nM, with a dramatic reduction of absorbance at 5000 nM (>80% reduction compared to the control). Nevertheless, the combination of 500 nM SAHA with 10mM ALCAR reveled a synergistic interaction, with a 46% reduction in absorbance. We then analyzed the effects on apoptosis induction, as determined by the percentage of cells with a sub-G1 DNA content. MS-275 dose-dependently induced apoptosis in HL-60 cells (4.2%, 17.1%, 60.8%, and 87.5% in the presence of 100, 500, 1000, 5000 nM of MS-275, respectively). Conversely, SAHA induced minimal apoptosis (< 10%) at concentration ranging from 100 to 1000 nM, although > 75% of cells became apoptotic after treatment with the compound at 5000 nM. In summary, our results show that the HDAC-I MS-275 is a potent inhibitor of leukemic cell growth, capable of inducing apoptosis particularly in cell lines derived from myeloid leukemia and MM. Preliminary studies exploring the combined use of ALCAR with the SAHA support a potential anti-neoplastic synergism in selected hematological malignancies. Disclosures: Petrucci: Celgene: Honoraria; Janssen Cilag: Honoraria. Pisano: Sigma-Tau: Employment. Tafuri: Sigma-Tau: Research Funding.

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