Radiosensitivity

Ceramide has been implicated as an important component of radiation-induced apoptosis of human prostate cancer cells. We examined the role of the sphingolipid metabolites--ceramide, sphingosine, and sphingosine-1-phosphate--in susceptibility to radiation-induced apoptosis in prostate cancer cell lines with different sensitivities to gamma-irradiation. Exposure of radiation-sensitive TSU-Pr1 cells to 8-Gy irradiation led to a sustained increase in ceramide, beginning after 12 h of treatment and increasing to 2.5- to 3-fold within 48 h. Moreover, irradiation of TSU-Pr1 cells also produced a marked and rapid 50% decrease in the activity of sphingosine kinase, the enzyme that phosphorylates sphingosine to form sphingosine-1-phosphate. In contrast, the radiation-insensitive cell line, LNCaP, had sustained sphingosine kinase activity and did not produce elevated ceramide levels on 8-Gy irradiation. Although LNCaP cells are highly resistant to gamma-irradiation-induced apoptosis, they are ...

Cellular radiosensitivity is directly correlated with the mechanism of DNA repair, in which p53 protein plays a major role. In this context, this study correlated cell death with p53 expression in lymphocytes irradiated in vitro with different doses of gamma-radiation. For this, peripheral blood samples were collected from 10 healthy subjects. Each sample was divided in aliquots and, separately, irradiated with doses of 0.5; 2 and 4 Gy. After this, peripheral blood mononu-clear cells (PBMCs) were isolated and cultivated during 72 hours in 5% CO 2 at 37˚C without mi-togen stimulation. The expression of p53 protein was evaluated by flow cytometry. In parallel, cell viability was determined by trypan blue staining. Statistical analysis was performed using analysis of variance (ANOVA), differences were considered as statistically significant when p < 0.05. The results showed an increase of p53 expression with the absorbed dose, which was proportional to cell death, suggesting that p53 can be used as bioindicator of individual radio-sensitivity.

Intrinsic radiosensitivity of normal and tumour tissues has been shown to be an independent prognostic factor for patients&apos; response to radiotherapy. This study compares the real-time cell-impedance sensing (RT-CES) assay with the conventional clonogenic assay in terms of in-vitro radiosensitivity. One objective in this study was to predict in-vivo response to gold nanoparticle (GNP) treatment on the basis of in-vitro RT-CES testing results. Four adenocarcinoma cancer cell lines were tested using both the RT-CES and the clonogenic assays. Cell-survival curves were plotted, and the mean SF2 values obtained by these two different assay methods were compared using ANOVA. Radiation sensitivities obtained in-vitro were then compared with the in-vivo results. On the basis of the measurement of cell colonies, the RT-CES assay has similar radiosensitivity to the clonogenic assay, but significantly shortens the testing time from 14-21 days to only 72 h. Intrinsic GNP enhanced radiation ...

The cancer-prone neurodegenerative disorder, ataxia telangiectasia (A-T), results from mutations of ATM (ataxia telangiectasia mutated). Individuals with A-T are also hypersensitive to ionizing radiation (IR). Cultured cells from A-T individuals or Atm2/2 mice have cell cycle and growth defects and are generally considered radiosensitive. However, it has been shown recently that cell populations in the Atm2/2 central nervous system are

... Titre du document / Document title. The dose-mortality response of Tribolium species to gamma irradiation throughout ontogeny. Auteur(s) / Author(s). SELMAN BJ ; MAHBUB HASAN (1) ; Affiliation(s) du ou des auteurs / Author(s) Affiliation(s). (1) Univ. Newcastle upon Tyne, dep ...

Background:Nuclear texture analysis measures phenotypic changes in chromatin distribution within a cell nucleus, while the alkaline Comet assay is a sensitive method for measuring the extent of DNA breakage in individual cells. The authors aim to use both methods to provide information about the sensitivity of cells to ionizing radiation.Nuclear texture analysis measures phenotypic changes in chromatin distribution within a cell nucleus, while the alkaline Comet assay is a sensitive method for measuring the extent of DNA breakage in individual cells. The authors aim to use both methods to provide information about the sensitivity of cells to ionizing radiation.Methods:The alkaline Comet assay was performed on six human bladder carcinoma cell lines and one human urothelial cell line exposed to γ-radiation doses from 0 to 10 Gy. Nuclear chromatin texture analysis of 40 features was then performed in the same cell lines exposed to 0, 2, and 6 Gy to explore if nuclear phenotype was related to radiation sensitivity.The alkaline Comet assay was performed on six human bladder carcinoma cell lines and one human urothelial cell line exposed to γ-radiation doses from 0 to 10 Gy. Nuclear chromatin texture analysis of 40 features was then performed in the same cell lines exposed to 0, 2, and 6 Gy to explore if nuclear phenotype was related to radiation sensitivity.Results:Comet assay results demonstrated that the cell lines exhibited different levels of radiosensitivity and could be divided into a radiosensitive and a radioresistant group at >6 Gy. Using stepwise discriminant analysis, a subset of important nuclear texture features that best discriminated between sensitive and resistant cell lines were identified A classification function, defined using these features, correctly classified 81.75% of all cells into their radiosensitive or radioresistant groups based on their pretreatment chromatin phenotype. Posttreatment chromatin changes also varied between cell lines, with sensitive cell lines showing a relaxed chromatin conformation following radiation, whereas resistant cell lines exhibited chromatin condensation.Comet assay results demonstrated that the cell lines exhibited different levels of radiosensitivity and could be divided into a radiosensitive and a radioresistant group at >6 Gy. Using stepwise discriminant analysis, a subset of important nuclear texture features that best discriminated between sensitive and resistant cell lines were identified A classification function, defined using these features, correctly classified 81.75% of all cells into their radiosensitive or radioresistant groups based on their pretreatment chromatin phenotype. Posttreatment chromatin changes also varied between cell lines, with sensitive cell lines showing a relaxed chromatin conformation following radiation, whereas resistant cell lines exhibited chromatin condensation.Conclusions:The authors conclude that the alkaline Comet assay and nuclear texture methodologies may prove to be valuable aids in predicting the response of tumor cells to radiotherapy. © 2006 International Society for Analytical CytologyThe authors conclude that the alkaline Comet assay and nuclear texture methodologies may prove to be valuable aids in predicting the response of tumor cells to radiotherapy. © 2006 International Society for Analytical Cytology

A predictive assay of normal tissue radiosensitivity could benefit &amp;#39;treatment tailoring&amp;#39; of radiotherapy for certain categories of tumour. The use of present clonogenic cell survival assays for this purpose would be impractical in routine clinical practice because of the lengthy assay time. Fluorescence in situ hybridization (FISH) using whole chromosome probes on metaphases was investigated as a potential substitute. Eight human fibroblast cell strains with a range of radiosensitivities were tested. For each strain, cell survival curves were determined and correlated with chromosome aberrations detected by FISH performed on metaphase cells collected 52 h after irradiation. A whole chromosome probe for chromosome 4 was used for all cell strains. The results revealed an increase in the percentage of metaphases with aberrant chromosomes (translocations and/or breaks) with increasing radiation dose for all strains. For the more radiosensitive cell strains there were relatively more aberrant metaphases for a given radiation dose when compared with fibroblasts from a normal donor. The relationship between surviving fraction and chromosome aberrations showed some variation between strains, but a linear regression for all data showed a highly statistically significant correlation (r = 0.89, p &amp;lt; 0.0005). These results suggest that an assay of chromosome damage using FISH could substitute for the clonogenic assay to predict the radiation sensitivity of human fibroblasts.

The ability of the sister chromatid exchange (SCE) assay to detect heterogeneity in intrinsic radiation sensitivity was investigated. In order to identify tumour cell subpopulations, frequency histograms of cis-diamminedichloroplatinum (II) (cPt)-induced SCEs were generated and compared to those from cultures that had been irradiated 96 h before drug treatment. The results suggested that subpopulations with different radiosensitivities were present in nine of 18 human primary tumour cell cultures evaluated. When the effects of prior irradiation on the subsequent X-ray survival response and on cPt-induced SCE frequency histograms were compared, a good correlation was obtained between the two assays regarding the prediction of heterogeneity in radioresponse. These results suggest that primary cultures can contain both radiation-sensitive and radiation-resistant cells, and thus heterogeneity in intrinsic radiosensitivity may exist in human solid tumours.

A substantial proportion of women with breast cancer exhibit an abnormally high radiosensitivity as measured by the frequency of chromatid breaks induced in G2-phase, PHA stimulated lymphocytes. Chromatid break frequencies were compared for a cohort of previously untreated sporadic breast cancer patients and hospital outpatient controls. In the breast cancer group 46% showed high radiosensitivity compared to 14% of controls (P&lt; 0.001). Comparison of those breast cancer patients with a high G2 radiosensitivity (G2RS) versus those with a low G2RS showed no difference in menopausal status or age but the high G2RS group had on average a lower score on the Nottingham Prognostic Index. Predicted survival in the high G2RS group at 15 years was 55% compared to 36% for the low G2RS group. Furthermore, 81% of tumours from the high G2RS were oestrogen receptor positive compared to 45% from the low G2RS group. Thus high G2RS identifies a sub-population of patients with distinctive tumour cha...

The effect of tamoxifen on the radiosensitivity of an estrogen receptor positive (ER+) and an estrogen receptor negative (ER−) breast carcinoma cell line was studied in vitro. Tamoxifen concentrations of 1 and 5 μM inhibited the proliferation of ER+ MCF-7 cells but had little effect on the growth of ER− MDA-MB-231. A 48 hr incubation in tamoxifen increased the proportion of G0/G1 MCF-7 cells, but minimally altered the cell cycle kinetics of MDA-MB-231 cells. Tamoxifen resulted in a small but significant increase in the mean inactivation dose of subconfluent cultures of the ER+ cells but had no effect on the ER− cells. The predominant change for MCF-7 cells was a decrease in the linear damage coefficient, alpha. This was not associated with any enhanced capacity to recover from split radiation fractions. There was no difference in radiosensitivity comparing irradiated log-phase to immediately plated plateau-phase cells. However, 24 hr delayed plating of irradiated plateau-phase cells resulted in decreased radiosensitivity of a magnitude comparable to that seen with tamoxifen. Quantitation of DNA strand fragmentation revealed no difference in the amount of single or double strand break induction nor the kinetics of strand break repair for cultures irradiated with or without tamoxifen. We conclude that tamoxifen results in a small decrease in the radiosensitivity of proliferating hormone responsive breast carcinoma cells and this effect appears to be most related to delay in cycle progression after release from tamoxifen inhibition. © 1993 Wiley-Liss, Inc.

It is assumed that hemodialysis treatment can diminish the levels of genetic damage in circulating lymphocytes by cleaning the blood of uremic toxins that cause oxidative stress. However, the hemodialysis process by itself may also induce genomic damage by producing reactive oxygen species (ROS). We conducted a follow-up study in a group of 70 hemodialysis patients followed for a mean time of 15 months. We investigated the effect of exposure time in hemodialysis on the levels of genetic damage in peripheral blood lymphocytes using the micronucleus assay. In addition, genetic damage after in vitro irradiation with 0.5 Gy was also analyzed to evaluate changes in radiosensitivity. Our results showed that, at the end of the study, there was a decrease in both the basal levels of genetic damage (9.9 ± 1.0 vs. 7.6 ± 0.7) and radiosensitivity values (38.5 ± 3.0 vs. 27.6 ± 2.4). We conclude that hemodialysis procedures may act as an ameliorating factor reducing the genetic damage present in chronic kidney disease patients.