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Results for “Radiosensitivity”

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At least 973 records · Page 54Linked to original sources

PubMed2004

Radiosensitization of a human soft tissue sarcoma cell line US8-93 (mt-p53) with the oxidizer sodium peroxodisulfate.

Side effects make it necessary to seek new radiosensitizers with low systemic actions. Sodium peroxodisulfate is a strong oxidizer classified as a safe agent with low systemic effects. We have examined the effect of this oxidizer on the radiosensitivity of the radioresistant human soft tissue sarcoma cell line US8-93 (mt-p53). The effects of peroxodisulfate (0.02-3.0 mM) with or without irradiation were studied by clonogenic survival assay, comet assay and the induction of apoptosis. We found sodium peroxodisulfate to be nontoxic for US8-93 up to a concentration of 0.1 mM. The combination of 0.1 mM sodium peroxodisulfate and irradiation showed a slight radiosensitizing effect with an enhancement factor of up to 1.5. This was coupled with an increase in apoptosis from 12 to 22% and an inhibition of repair of irradiation-induced DNA damage. Incubation with concentrations between 0.1-1.0 mM sodium peroxodisulfate resulted in a strong decrease of clonogenic survival with an IC50 of 0.28 mM. This was correlated with an increase in cross links. Furthermore, a strong additive effect was observed for the combination of 0.3 mM sodium peroxodisulfate and irradiation resulting in an increase in enhancement ratio from 1.3 at 2 Gy to 3.1 at 6 Gy (p</=0.08). However, no further increase in apoptosis was detected. Our results implicate sodium peroxodisulfate to be a potentially useful agent to improve the radiobiological efficacy in radioresistant soft tissue sarcomas as exemplified for the cell line US8-93.

Apoptosis↗

PubMed2004

Relationship between radiosensitivity and normal tissue complications in Saudi cancer patients treated with radiotherapy.

PURPOSE: To assess the variations in radiosensitivity, its relationship with clinical complications and the potential application of predictive testing in Saudi radiotherapy patients. MATERIALS AND METHODS: Forty-one patients included in this study, during (17) or after (24) their radiation treatment for head and neck (26), breast (9), gynecological (3) or other (3) cancer. Skin fibroblasts were established and radiosensitivity was measured. The surviving fraction at 2 Gy (SF2) was calculated and compared to the maximum grade of acute (erythema, desquamation, mucositis, ulceration) and late reactions (atrophy, fibrosis, xerostomia, telangiectasia). Follow-up ranged between 12 and 178 months (median 30). RESULTS: SF2 ranged between 0.16 and 0.56 (mean 0.34). The inter-patients coefficient of variation (CV) was 26%. The intra-patient CV was 18%. There was a statistically significant correlation between fibroblasts SF2 and the maximum grade of late (p = 0.012; 40 patients), but not acute complications (p = 0.70; 36 patients). There was no correlation between acute and late reactions (p > 0.05; 34 patients). CONCLUSIONS: These data revealed wide variations in cellular radiosensitivity that correlated with late reactions to radiation treatment. Radiotherapy patients, particularly those at risk to sustain severe complications may well benefit from individualizing the doses prescription. However, a predictive test alternative to SF2 is required.

Journal Article↗

PubMedDate not supplied

Iodinated nitroimidazoles as radiosensitizers.

Four different nitroimidazole derivatives, with up to two iodine atoms on the imidazole ring, were investigated for their radiosensitizing potency under hypoxic conditions, in order to test whether the introduction of iodine atoms increases the radiosensitizing potency of nitroimidazoles. Misonidazole and metronidazole were used as controls. Human colonic adenocarcinoma cells were incubated with the drugs at different concentrations and for different time-periods. Photon energies of 50 kV, 60 kV and 20 MV and total radiation doses of up to 20 Gy were used. The introduction of additional iodine atoms into the nitroimidazole derivatives resulted in a strong increase in cytotoxicity of the compounds. In parallel, there were indications that the radiosensitizing potency was also increased.

Adenocarcinoma↗

PubMed2005

[Effect of MAb225 on radiosensitivity of Tca8113 tongue squamous cell carcinoma].

OBJECTIVE: The purpose of this study was to invest the effect of epidermal growth factor receptor monoclonal antibody MAb225 on radiosensitivity of tongue squamous cell carcinoma cell Tca8113. METHODS: Tca8113 cells were treated with different concentrations of MAb225. Radiation dose survival curve was generated from clonogenic survival assay. SERPD0 and survival faction (SF2) was analysed by single hit multi-target (SHMT) radiobiological model using RADMEDIC software. Nude mice with Tca8113 tumor xenografts were treated with MAb225, radiation treatment or both of them. Tumor responses were assessed by tumor growth delay, and t test was used for statistical analysis. RESULTS: MAb225 enhanced the radiosensitivity of Tca8113 cells. SERD0 of Tca8113 cells treated with 0.5 mg/L MAb225 was 1.23. The survival fraction of cells treated with MAb225 was significantly decreased. Tumor radioresponse could be enhanced by MAb225 (P < 0.05). CONCLUSION: MAb225 could enhance radiosensitivity of tongue squamous cell carcinoma cell.

Animals↗

PubMedDate not supplied

Radiosensitization of CHO cells by two novel rhodium complexes under oxic and hypoxic conditions.

BACKGROUND: Tumour hypoxia severely limits the success of radiotherapy. Radiosensitization of hypoxic tumour cells by drugs is thus an important clinical issue. MATERIALS AND METHODS: Two novel ferrocene-containing beta-diketonato complexes of the transition metals rhodium and iridium were examined for their cytotoxic activity against Chinese hamster ovary (CHO) cells by MTT and clonogenic assays. The same complexes were also tested for their capacity to sensitize hypoxic CHO cells against 8 MeV photons. RESULTS: The IC50 for [Rh(fcta)(cod)] (I) and [Rh (fctca)(cod)] (II), where (fctfa) = ferrocenoylacetonato-4,4,4-trifluoro and (fctca) = ferrocenoyl-4,4,4-trichloro- and (cod) = 1,5-cyclooctadiene, were found to be 1.38 microM and 4.18 microM, respectively, closely resembling that of cisplatin which was found to be 1.21 microM. The rhodium (I) complex was identified as an effective anoxic radiosensitizer showing a dose-modifying factor (DMF) of 1.93 +/- 0.02, resembling cisplatin where the DMF was found to be 1.99 +/- 0.02. Small DMF's in the range of 1.10 were also found for cisplatin and the rhodium (I) complex under aerobic conditions, but these were not statistically significant. The DMF for the iridium complex was small and found to be 1.06 +/- 0.04. CONCLUSION: The cytotoxicity and radiosensitizing properties of the rhodium (I) complex are very similar to cisplatin and show considerable potential for clinical application.

Animals↗

PubMed2006

[Cytotoxicity of pentoxifylline and its effect on human hepatoma cell line Hep3b radiosensitivity].

OBJECTIVE: To investigate the effects of pentoxifylline (PTX) on radiation induced-cell cycle redistribution and radiosensitivity of human hepatocellular carcinoma cell line Hep3b. METHODS: MTT assay was performed to evaluate the cytotoxicity of PTX on p53-defective human hepatocellular carcinoma cell line Hep3b and clonogenic assay employed to observe its effects on the radiosensitivity of the cells quantified by calculating the sensitive enhancement ratio (SER). Flow cytometry was performed to observe the cell cycle changes of Hep3b cells in response to X-ray irradiation and the interventional effect of PTX. RESULTS: The cytotoxicity of PTX on the cells increased in a dose-dependent manner following a 48-hour treatment, with the optimal dose range of 1-5 mmol/L. A sub-toxic dose of PTX at 2 mmol/L was then used in subsequent experiments. Clonogenic survival assays up to 12 Gy demonstrated that p53-defective Hep3b cells (SER of 2.68+/-0.24) were sensitized by PTX (2 mmol/L). PTX (2 mmol/L) treatment following exposure to irradiation (6 Gy) resulted in abrogation of radiation-induced G(2)/M arrest of Hep3b cells, and the proportions of Hep3b cells in G(2)/M phase were 86.8% and 14.8% after exposure to 6 Gy alone and 6 Gy plus 2 mmol/L PTX, respectively. CONCLUSION: Radiosensitization by PTX is possibly associated with the abrogation of G(2)/M arrest in Hep3b cells following radiation exposure, suggesting that potential clinical application of PTX may enhance the efficacy of radiotherapy against hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

PubMed2006

[Radiosensitivity changes of nasopharyngeal carcinoma cells with different levels of differentiation after treatment with chemotherapeutic agents].

OBJECTIVE: To examine the changes of radiosensitivity of CNE1, a well differentiated squamous cell line of nasopharyngeal carcinoma (NPC), and CNE2, a poorly differentiated squamous cell line of NPC, after treatment with chemotherapeutic agents. METHODS: CNE1 and CNE2 cells with and without treated by adriamycin (ADM) were irradiated by X-ray and the radiosensitivity changes of ADM-treated cells were analyzed according to the cell survival curve generated by colony formation assay. RESULT AND CONCLUSION: Radiosensitivity of CNE1 cells increased after ADM treatment, but that of CNE2 cells decreased, suggesting that different treatment regimens should be planned for advanced squamous cell NPC of different pathological types.

Antineoplastic Agents↗

PubMed2006

[Influence of survivin gene repression by RNA interference on the radiosensitivity and chemosensitivity to cisplatin of cervical cancer cell HeLa].

OBJECTIVE: To observe the effect of survivin gene repression by RNA interference (RNAi) on the radiosensitivity and the chemosensitivity to cisplatin of cervical cancer cell HeLa. METHODS: The recombined eukaryotic expression plasmid pSilencer2.1-s2 containing human survivin gene small interference RNA (siRNA) was transfected into human cervical cancer cell line HeLa by using lipofectamine 2000. The expression of survivin gene mRNA and its protein was detected by semi-quantitative RT-PCR and western blot respectively. The changes of caspase-3 activity was assessed by kinase activity test. Cell apoptosis was examined by flow cytometry. The changes of cell radiosensitivity was observed by plate clone formation assay. Cell viability was examined by methyl thiazolyl tetrazolium (MTT) assay and 50% inhibitive concentration (IC(50)) of cisplatin was examined also. RESULTS: Compared with the cells which were transfected with negative control plasmid (HeLa-NC), pure plasmid (HeLa-U6 neo) and un-transfected cells (HeLa), the expression level of survivin gene mRNA and protein declined evidently in the cells transfected with pSilencer2.1-s2 plasmid (HeLa-s2), the expression inhibitory rates were (62.8 +/- 0.3)% and (60.1 +/- 0.5)%; the caspase-3 activity was enhanced and A(405) was 1.261 +/- 0.043 (P < 0.05); the apoptotic rate was increased obviously (29.23 +/- 1.41)% (P < 0.05). At the same dose of radiation, clone formation rate declined significantly (P < 0.05); at the same concentration of cisplatin, cell viability declined sharply and the IC(50) of cisplatin was (0.873 +/- 0.021) microg/ml (P < 0.05). CONCLUSION: Survivin gene repression by RNAi can enhance caspase-3 activity, induce cell apoptosis, significantly increase the radiosensitivity and chemosensitivity to cisplatin in human cervical cancer cell line HeLa.

Antineoplastic Agents↗

PubMed1991

Fluorodeoxyuridine-mediated modulation of iododeoxyuridine incorporation and radiosensitization in human colon cancer cells in vitro and in vivo.

A study was conducted to assess the potential of 5-fluoro-2'-deoxyuridine (FdUrd) to increase the incorporation and radiosensitizing properties of 5-iodo-2'-deoxyuridine (IdUrd) using HT29 human colon cancer cells both in vitro and in nude mice bearing these tumors as xenografts. The purpose of this study was to assess (a) whether FdUrd could increase IdUrd efficacy using clinically achievable concentrations of drugs; (b) the relationships among radiosensitization, DNA damage and repair, and analogue incorporation; and (c) whether FdUrd improved the selectivity of IdUrd incorporation into tumor cells compared to normal tissues. It was found that FdUrd, at clinically achievable concentrations (1-100 nM), significantly increased IdUrd incorporation under all conditions but particularly when the IdUrd concentration was less than or equal to 10 microM. FdUrd increased IdUrd-mediated radiosensitization in proportion to the increase in IdUrd incorporation. FdUrd potentiated the ability of IdUrd to increase radiation-induced DNA double-strand breaks and to slow their repair. When IdUrd alone (100 and 200 mg/kg/day) was infused into nude mice bearing tumors, the extent of thymidine replaced in the tumor was 1.6 +/- 0.4 (mean +/- SE) and 2.5 +/- 0.4%, respectively. The combination of FdUrd (0.1 mg/kg/day) and IdUrd (100 mg/kg/day) increased the incorporation in the tumor to 5.3 +/- 0.9% with less toxicity than resulted from the use of 200 mg/kg/day of IdUrd alone. These data show that FdUrd is an effective biomodulator, because, for the same extent of normal tissue incorporation, the combination of IdUrd and FdUrd produces significantly greater incorporation into the tumor compared to the use of IdUrd alone. Furthermore, they suggest that the regional application of FdUrd with IdUrd, either through the use of regional infusions or in combination with focused irradiation, could potentially improve the outcome of treatment of localized gastrointestinal cancer.

Animals↗

PubMed1991

[Synthesis of 1-substituted nitroimidazoles and its evaluation as radiosensitizing agents].

The synthesis of various substituted nitroimidazoles with lipophilic and hydrophilic side chains as potential radiosensitizing agents is described. The starting material employed was 4(5)-nitroimidazole, which was alkylated via the sodium salt with various chloro-methylated, substituted alcohols and esters, in order to obtain analogues of misonidazole, metronidazole and desmethylmisonidazole of known radiosensitizing and bactericidal activity. Some final products were assayed for their radiosensitizing properties giving negative results under the testing conditions used.

In Vitro Techniques↗

PubMed1991

[Histopathological evaluation of the radiosensitizing effects of an intratumoral injection of BrdU for rectal cancer].

We delivered preoperative radiotherapy with intratumoral injection (ITI) of radiosensitizer, 5-bromodeoxyuridine for patients with locally advanced cancer originating in lower rectum. We identified immunohistochemically the tumor cells that incorporated BrdU, and evaluated the radiosensitizing effect of BrdU histopathologically. (1) BrdU-labeled nuclei of cancer cells were identified in twenty-three cases out of 24 (96%). Mean labeling index was 18.5%, and tended to decrease as time progressed. (2) The parameters representing volume of residual tumor nests (Tumor Nest Index) or degrees of tumor extension (Depth of Extramural Tumor and Depth of Extramural Fibrosis) for patients with ITI were compared to those for patients without ITI. Those parameters tended to decrease when ITI was combined with radiotherapy. However, the difference was not significant statistically. Intratumorally injected BrdU can incorporate with cancer cells, but a methodological invention is required for yielding clinically measurable radiosensitization.

Adenocarcinoma↗

PubMed1991

Tumor radiosensitivity prediction by the cytokinesis-block micronucleus assay.

An in vivo to in vitro cytokinesis-block micronucleus assay technique using cytochalasin B (Cyt-B) was established in xenografted human and murine tumors, and the correlation between radiosensitivity measured by this assay and that measured by a colony-forming assay was investigated. Tumors were irradiated in situ, excised immediately, and disaggregated to single cells that were plated for the micronucleus and colony-forming assays. Some of the tumor cells were irradiated in vitro rather than in vivo. For the micronucleus assay, Cyt-B (0.5-3 micrograms/ml) was added to dishes soon after plating or in vitro irradiation and the cells were subsequently fixed and stained at intervals (12-144 h). The micronucleus frequency in binucleate cells was evaluated under conditions of maximum yield of the binucleate cells. The micronucleus frequency after irradiation was quite variable depending on the tumor type and the average number of micronuclei per single binucleate cell after 4 Gy ranged from 0.2 to 1.4. The results of in vitro irradiation were not significantly different from those of in vivo irradiation for all tumors. A good correlation was found between the radiosensitivity determined by the micronucleus assay and that found with the colony-forming assay in six human tumors (r = 0.94 approximately 0.98) but not in four murine tumors because of one exceptional tumor. When this tumor was excluded, a correlation was also found for the remaining nine tumors (r = 0.62 approximately 0.96). These results indicated that the cytokinesis-block micronucleus assay has some promise as a rapid predictive assay of radiosensitivity.

Animals↗

PubMed1991

Radiosensitization of human T-cell leukemia by thymidine and 41.8 degrees C hyperthermia in vitro.

This study tested whether thymidine, a naturally occurring nucleoside metabolite, could increase the sensitivity of human T-cell neoplasms to ionizing irradiation and whether adding 41.8 degrees C hyperthermia (X 1 h) to the combination of thymidine and irradiation would further enhance killing of cells by radiation. The magnitude of cytotoxicity induced directly by thymidine was also evaluated. Finally, the ability of 2'-deoxycytidine to prevent thymidine-induced cytotoxicity and radiosensitization was studied. Using JM and MOLT3, two human T-cell acute lymphoblastic leukemias, it was found that thymidine itself was cytotoxic and the toxicity appeared rapidly upon exposure to the drug (i.e., at 4 h). Thymidine caused significant radiosensitization, and thymidine plus 1 h of 41.8 degrees C hyperthermia enhanced radiation-induced killing significantly more than did thymidine or hyperthermia separately. The addition of 2'-deoxycytidine only partly reversed thymidine-induced killing and did not prevent thymidine-induced radiosensitization. The applicability of these results to the clinical management of T- and null-cell malignancies is discussed, as is the presumed mechanistic basis for these observations relative to deoxyribonucleoside metabolism, NAD metabolism, and inhibition of poly(ADP-ribose) polymerase.

Cell Survival↗

PubMed1990

Radiosensitivity of CD4 or CD8 positive human T-lymphocytes by an in vitro colony formation assay.

The recent development of an in vitro lymphocyte colony assay makes it possible to examine variations in the radiosensitivity of humans using peripheral blood lymphocytes (PBL) instead of the skin fibroblast assay. Our recent study (M. Hakoda et al., Mutat. Res. 197, 161-169, 1988) showed that most of the colonies consisted of lymphocytes bearing CD4 or CD8 antigens. Since the fraction of CD4+ and CD8+ cells in PBL differs among individuals, we suspected that individual radiosensitivity might be biased by the different subset frequencies if the dose-survival curves of the CD4+ and CD8+ cells were different from each other. In the present study, CD4+ (helper/inducer T) and CD8+ (suppressor/cytotoxic T) lymphocytes were isolated from PBL and their dose-survival curves were determined. The results showed that the D10 (dose required to reduce the surviving fraction to 10%) was similar for these two types of cells [3.13 +/- 0.10 Gy (mean +/- SD) for CD4+, 3.34 +/- 0.50 Gy for CD8+ and 3.14 +/- 0.17 Gy for the unsorted cells], supporting the use of the whole PBL population for the screening of individuals with altered radiosensitivity.

Adult↗

PubMed1990

Modulation of IdUrd-DNA incorporation and radiosensitization in human bladder carcinoma cells.

5' Amino-5'-deoxythymidine (5'-AdThd) has been demonstrated previously to antagonize dTTP-mediated feedback inhibition of purified thymidine kinase from 647V, a human bladder cancer cell line. Low concentrations of 5'-AdThd (3-30 microM) have also been shown to stimulate cellular uptake of iododeoxyuridine (IdUrd) in 647V cells at clinically relevant IdUrd concentrations (2 microM). We report that the combination of 30 microM 5'-AdThd plus 2 microM IdUrd results in a significant increase of IdUrd replacement of thymidine (dThd) (18%) in the DNA of 647V cells over that obtained by exposure to 2 microM IdUrd alone (7.9%). However, increasing the 5'-AdThd concentration to 300 microM inhibited the incorporation of IdUrd into DNA (3%). IdUrd-induced radiosensitization of 647V cells, as measured by clonogenic survival, was enhanced by coincubation with 30 microM 5'-AdThd, while 300 microM 5'-AdThd reduced the IdUrd radiosensitization. Additionally, radiation-induced single strand break generation when IdUrd was incorporated into 647V DNA, as measured by rapid alkaline elution, was also enhanced by coincubation with 30 microM 5'-AdThd, while 300 microM 5'-AdThd resulted in a decrease in the number of single strand breaks produced. In T24, another bladder cancer cell line, and SV-HUC-TT1, a tumorigenic cell line derived from SV-HUC, 3-10 microM 5'-AdThd was also able to enhance IdUrd replacement of dThd in DNA. However, no stimulation of dThd replacement by 5'-AdThd occurred in SV-HUC, a prototypic "normal" bladder urothelial cell line. Since 5'-AdThd is not a substrate for mammalian thymidine kinase and has little or no cytotoxicity in vitro and in vivo, it may be a selective modulator of IdUrd radiosensitization of human bladder carcinoma and should be tested in vivo.

Carbon Radioisotopes↗

PubMed1990

Radiosensitivity increases with differentiation status of murine hemopoietic progenitor cells selected using enriched marrow subpopulations and recombinant growth factors.

The radiosensitivity of populations of colony-forming cells (CFC) in murine bone marrow was investigated using different recombinant colony-stimulating factors (CSFs; murine IL-3 and granulocyte-macrophage CSF and human granulocyte CSF), or purified murine macrophage CSF. With unfractionated normal bone marrow the CFC increased in radiosensitivity as they progressed through the granulocyte lineage. The D0 values ranged from 129 +/- 12 cGy for CFC stimulated with GM-CSF down to 42 +/- 2 cGy after stimulation with G-CSF. IL-3 stimulated a CFC population which gave the only survival curve with a shoulder (n = 1.9 +/- 0.3). With semipurified populations of primitive or bipotential CFC, D0 values were generally lower with respect to the equivalent values for unpurified bone marrow (range 62 +/- 7 cGy to 135 +/- 7 cGy). Changes in cluster/colony ratio and colony morphology together possibly with products of accessory cells influence the interpretation of the radiosensitivity parameters.

Animals↗

PubMed1990

[Radiosensitization of mouse intestinal epithelial cells with BudR].

For the radiosensitization of the repair rich epithelial cells of small intestine, BudR (B.U.) was continuously infused into mice. Its uptake into the DNA, as shown by the substitution rate (S.R.) of thymine to B.U., was dose-dependent in low dose, but above the 4 mg/d/head it did not increased. The radiosensitization effect was assayed by the clonogenecity of the cells, and (1) the repair capacity (recovery factor, RF.) of the cells and (2) the isoeffect dose (I.D) were obtained. From these data, their enhancement ratios (E.R) were estimated. E.R. by R.F. increased remarkably both in low dose and in low S.R., but showed the plateau at about 10 level after 4 mg/d/h of dose or 10% of S.R. Whereas E.R. by I.D. increased linearly in dose or it did quadratically in S.R. From these results, it was discussed that radiosensitization by debromozation of B.U. was seen in low dose, and the direct cytocidal effect of B.U. became dominant with the dose-increase. Also the clinical application of B.U. was discussed in cell kinetical aspect of B.U. labelling as well as the progress of infusion techniques.

Animals↗

PubMed1990

Relationship between radiosensitivity and metallothionein content in clones from a mouse squamous cell carcinoma.

The relationship between intrinsic radiosensitivity and metallothionein (MT) level in several clones isolated from a mouse squamous cell carcinoma was studied. Dose-survival curves for exponentially growing cells assayed by the soft-agar colony method were fitted to the linear-quadratic model by the least-squares method. Intrinsic radiosensitivity was expressed as the mean inactivation dose (D) calculated by the parameters alpha and beta. The D of the clones ranged from 1.6 to 3.9 Gy. A significant negative correlation was obtained between individual D and MT levels determined by the 203Hg-binding assay when expressed as MT content per cell; however, no correlation was obtained when the levels were expressed as MT content per unit cellular volume. The D of the parent cell line MSCC was 2.0 Gy, and that of the most radioresistant clone R1 was 3.9 Gy. Metallothionein content was 315 and 37 Hg-bound pmol/10(6) cells for MSCC and R1 cells, respectively, and thus D was not positively correlated with the level of MT. Metallothionein content of MSCC and R1 cells was elevated to 2304 and 854 Hg-bound pmol/10(6) cells, respectively, by cadmium treatment. Both MSCC and R1 cells with elevated MT content became more resistant to cadmium toxicity. However, the D's of the two cell lines were identical to those of the untreated controls despite the elevated MT content. These results suggest that, at least in this tumor, the endogenous MT level is not a major factor in determining intrinsic radiosensitivity of aerated cells.

Animals↗