SEARCH · PubMed Health

Results for “Radiosensitivity”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources

PubMed2004

Functional consequences of ATM sequence variants for chromosomal radiosensitivity.

The ATM [for ataxia-telangiectasia (A-T) mutated] protein plays a key role in the detection and cellular response to DNA double-strand breaks. Several single-nucleotide polymorphisms (SNPs) have been described in the ATM gene; however, their association with cancer risk or radiosensitivity remains to be fully established. In this study, the functional consequences of specific ATM SNPs on in vitro radiosensitivity, as assessed by micronuclei (MN) formation, were measured in lymphoblastoid cell lines established from 10 breast cancer (BC) patients carrying different ATM missense SNPs, six A-T patients, six A-T heterozygotes (A-T het), and six normal individuals. The BC, A-T het, and A-T cell line groups showed significantly higher mean levels of MN formation after exposure to ionizing radiation (IR) than did the group containing normal cell lines, with similar levels in the BC and A-T het groups. Within the BC lines studied, the group composed of the six carrying the linked 2572T>C (858F>L) and 3161C>G (1054P>R) variants had a higher level of MN after IR exposure compared to that observed in the remaining four BC or in the normal cell lines. This increase was not related to the constitutive ATM mRNA level, which was similar in these BC and the normal cell lines. Our results indicate that alterations in the ATM gene, including the presence of heterozygous mutations and the 2572C and 3161G variant alleles, are associated with increased in vitro chromosomal radiosensitivity, perhaps by interfering with ATM function in a dominant-negative manner.

Ataxia Telangiectasia↗

PubMed1986

Radiosensitization of human tumor cells by alpha-difluoromethylornithine.

The effect of polyamine depletion on the radiosensitivity of a human tumor cell line was investigated. CAL 18 A cells, derived from a breast carcinoma, were incubated with alpha-difluoromethylornithine (DFMO)--a specific and irreversible inhibitor of ornithine decarboxylase (ODC)--at a 1 mM or 10-mM concentration for either 1 hr or 24 hr and irradiated thereafter. Survival curves of exponentially growing cells revealed a moderate but significant enhancement of radiosensitivity as compared to untreated irradiated cells. Maximum radiosensitization was observed at a concentration of 10 mM after 1 hr incubation. Plateau-phase cells were used to study the effect of polyamine inhibition on repair of radiation-induced potentially lethal damage (PLD). DFMO enhanced the radiation response and significantly inhibited PLD repair in these cells. Measurement of ODC indicated that this enzyme was markedly inactivated upon brief incubation of CAL 18 A cells with DFMO, reflecting a depletion of polyamine synthesis. These results extend findings that have demonstrated enhancement of drug-induced cytotoxicity, and raise the possibility of clinical use of this substance for potentiation of radiation response.

Breast Neoplasms↗

PubMed1991

The effect of radiosensitizers on radio-immunotherapy, using 131I-labelled anti-CEA antibodies in a human colonic xenograft model.

Anti-CEA antibodies were used for radio-immunotherapy in an established LS174T colonic xenograft in nude mice. A single IV dose of either 131I-PK4S (polyclonal) or -A5B7 (monoclonal) antibody produced tumour regression, and significantly delayed subsequent tumour growth. Administration of a clearing second antibody, 24 hr post 131I-PK4S and at 5 times the dose, significantly reduced the therapeutic effect of radio-antibody alone. Tumours of mice given non-specific antibody or unlabelled anti-CEA antibody grew like those of untreated controls. In an attempt to enhance therapy without increasing dose, radiosensitizers normally employed with external beam radiation were used in combination therapy. When the hypoxic cell radiosensitizer misonidazole was combined with 131I-A5B7, it significantly prolonged tumour-growth inhibition over radio-antibody alone. Conversely, the therapeutic effect of either radio-antibody was significantly reduced when used in combination with the halogenated pyrimidine radiosensitizer 5-iododeoxyuridine. Neither sensitizer alone affected tumour growth.

Animals↗

PubMed2003

Perillyl alcohol mediated radiosensitization via augmentation of the Fas pathway in prostate cancer cells.

BACKGROUND: The management of hormone-insensitive locally advanced prostate cancer is difficult and complex and there is an urgent need for the development of effective chemotherapeutic agents intended for combination with currently available treatment modalities. METHODS: The present paper demonstrates the effectiveness of the monoterpene perillyl alcohol (POH) as potent radiosensitizer on DU145 and PC3 cell lines by performing clonogenic survival assays, cycle analysis, and assays to detect viability, apoptosis, and Fas receptor/ligand by flow cytometry. RESULTS: POH pretreatment resulted in a dose dependent sensitization to kill cell by radiation. Furthermore, POH treatment induced a transient G(2)/M arrest, enhanced the expression of the membrane bound form of the Fas ligand and sensitized the cells to Fas mediated apoptosis. CONCLUSIONS: The unique manner of radiosensitization in addition to its low toxicity profile makes POH a promising new agent for preclinical evaluation as a potential radiosensitizer in the treatment of prostate cancer.

Antineoplastic Agents↗

PubMed1996

Heterogeneity in radiosensitivity of human diploid fibroblasts from keloids and normal skins.

Colony-forming ability was employed in evaluating the susceptibility to in vitro gamma ionizing radiation in human diploid skin fibroblasts (HDF). Twelve pairs of HDF, each composed of fibroblasts from excised keloid lesion and local normal skin tissue as its control, were studied in patients with clinically persistent keloids. Parameters of radiosensitivity, both D0 and D10, and growth kinetics were examined. The radiosensitivity in three of the 12 keloids (25%) were demonstrated significantly increased than their counterpart controls, even though no difference in growth kinetics in between. Moreover, a broad range in the radiosensitivity of fibroblast cells was demonstrated and it is suggested that there is a great heterogeneity of cellular response to radiation in HDF.

Aged↗

PubMed1997

Radiosensitivity patterns of four human ovarian cancer cell lines in vitro.

Clinical evidence and the majority of experimental data suggest a cross-resistance between cisplatin and radiation in ovarian cancer. The authors are not aware of any report of a human ovarian cancer cell line for which the dose-response relationships to both radiation and chemotherapy including paclitaxel and cisplatin have been evaluated with the same methodology. The present study investigated the radiosensitivity profiles of four established human ovarian cancer cell lines in vitro using the ATP assay, which measures total cell kill. The CAOV-3 cell line showed the highest degree of radiosensitivity of the four cell lines. SKOV-3 cells were the most resistant. The BG-1 cell line, previously shown to be highly resistant to cisplatin but sensitive to paclitaxel, was distinctly sensitive to radiation. This was particularly true for the lower dosages (2-6 Gy). The four cell lines tested are a good representation of cell lines with different radiosensitivities. The different response patterns to cytotoxic agents and radiation, make the BG-1 cell line in particular an interesting candidate for future studies on mechanisms of resistance and combination effects between radiation and chemotherapy.

Dose-Response Relationship, Radiation↗

PubMed1997

Characterization of highly radiosensitive cell lines from a human ovarian small-cell cancer.

Cells were obtained at paracentesis from a patient with a rapidly growing ovarian tumor. A monolayer cell line (V7S), a xenograft tumor line (V7), and subsequently a xenograft-derived monolayer cell line (V7M) were established. Histological and immunohistochemical studies of the original tumor, xenograft, and cell lines provided a diagnosis of small-cell carcinoma of the ovary-which is consistent with the clinical course of the patient. V7S and V7M had a predominantly hypodiploid karyotype with a small tetraploid population. The V7M, which has been in long-term culture, also showed a nonrandom translocation involving chromosomes 1 and 14 and monosomy of X. Radiobiologically, V7S, V7, and V7M showed marked radiosensitivity with surviving fractions at 2 Gy, measured by clonogenic assay, of between 0.022 and 0.147. Split-dose experiments provided evidence that this radiosensitivity was not due to an inability in cellular repair. In vivo data from the xenograft (V7) revealed a highly radiosensitive tumor, corroborating the in vitro studies.

Carcinoma, Small Cell↗

PubMed1998

p53 mutations and presence of HPV DNA do not correlate with radiosensitivity of gynecological cancer cell lines.

OBJECTIVE: The correlation between p53 tumor suppressor gene mutations and the presence of high-risk human papillomavirus (HPV) DNA with the in vitro radiosensitivity of gynecological malignancies was studied in 26 cell lines derived from gynecological cancers of 23 patients. METHODS: Comparison of the intrinsic radiosensitivity was performed with mean inactivation dose (D) determined with the 96-well plate clonogenic assay. p53 mutations were investigated with polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) analysis and direct DNA sequencing, and the presence of HPV DNA was studied with PCR using HPV consensus primers. RESULTS: p53 mutations were found in 6 of 10 vulvar squamous cell carcinoma (SCC) lines. Nine vulvar and 1 vaginal SCC cell lines were HPV DNA negative and 1 vulvar cell line was HPV 16 positive. All 4 cervical SCC lines were HPV positive and possessed the wild-type p53. Three cell lines expressed HPV 16 and 1 HPV 68. Among 10 endometrial cancer cell lines, 2 cell lines with mutant p53 and 1 HPV 16 positive cell line were found. No correlation could be demonstrated between inactivation of the p53 gene and radiosensitivity in vitro; the cell lines were evaluated as one group or according to their anatomical origin or histology. CONCLUSION: Our results indicate that inactivation of the p53 gene through mutation or binding with HPV DNA does not increase the resistance of gynecological malignancies to ionizing radiation in vitro.

DNA, Viral↗

PubMed1997

Isolation of radiosensitive and radioresistant mutants from a medulloblastoma cell line.

Two mutant clones, one radiosensitive (OS-3) and one resistant (OR-5), were isolated from ONS-76 after screening 2400 clones by the replica micro-well technique. These two clones exhibited significantly different radiosensitivity, with D37 values of 4.7Gy in OR-5 and 1.7Gy in OS-3. After gamma irradiation (8Gy), OR-5 exhibited greater G2 arrest than sensitive clone OS-3. Administration of 5mM of caffeine resulted in greater cell killing in OR-5 than in OS-3, with an almost complete release of G2 block. These observations support the notion that the G2 block contributes to the repair process of DNA damage after irradiation. The present results suggest that clones with a large postirradiation G2 block may show a greater reduction in radiosensitivity if the G2 block is released artificially. The study of the mutant clones described herein may provide important clues to the mechanism by which glioma cells acquire radioresistance.

Caffeine↗

PubMed1997

Rare microsatellite polymorphisms in the DNA repair genes XRCC1, XRCC3 and XRCC5 associated with cancer in patients of varying radiosensitivity.

DNA repair defects might contribute both to cancer progression and to the extreme reactions to radiotherapy observed in approximately 5% of patients. Polymorphic microsatellites in three DNA repair genes, XRCC1, XRCC3 and XRCC5, were analyzed for possible linkage to cancer status or clinical radiosensitivity. XRCC1, 3 and 5 proteins are involved in single-strand DNA break rejoining, recombinational repair, and double-strand DNA break rejoining respectively. Mendelianly inherited microsatellite polymorphisms in these genes were analyzed in three groups: volunteers with no cancer history; radiosensitive cancer patients; cancer patients with acceptable reactions to radiotherapy. Rare heterozygous alterations in all three gene regions were found solely in the cancer subpopulation. Association testing between these rare polymorphisms and cancer status revealed a significant association for XRCC1 (P = 0.005), and XRCC3 (P = 0.004). There was also an association between these polymorphisms and clinical radiosensitivity for XRCC1 (P = 0.03), and XRCC3 (P = 0.005).

Adult↗

PubMed1984

Morphologic and histochemical studies on the differing radiosensitivity of ductular and acinar cells of the rat submandibular gland.

The submandibular glands of male rats were exposed to 50 Gy X-irradiation as a single dose, with or without pre-treatment with either alpha-adrenergic agonists (noradrenaline, phenylephrine) or a cholinergic antagonist (atropine). The effects were analyzed by morphometric, cytochemical and biophysical methods. When X-irradiated without drug pre-treatment, many serous epithelial cells of the intralobular convoluted ducts displayed morphologic evidence of irreversible radiation damage, in contrast to neighbouring mucous and other cells which were unaffected. The effect was maximal 96 h after irradiation. Serous cells from animals irradiated after pre-treatment with atropine showed much more wide-spread injury than those of animals exposed to X-irradiation only. In contrast , serous cells suffered considerably less damage if their secretory granules had been depleted 1 or 2 h before irradiation with either noradrenaline or phenylephrine. Other epithelial cells showed no modulation of their slight radioresponsiveness by these drugs. The observations were substantiated by morphometry of three cell types: (a) mucous cells, (b) non-granulated serous and intralobular striated duct cells, and (c) granulated serous cells. The findings suggest that the striking radiosensitivity of salivary gland serous epithelial cells is linked to their content of secretory granules. These granules are rich in heavy metals, as demonstrated cytochemically with the sulphide silver method (SSM). Using particle-induced X-ray emission ( PIXE ) spectroscopy, the principal metals were shown to be Zn, Mn and Fe. It is conceivable that membranes which enclose organelles rich in metals with the ability to form redox systems (e.g. Fe2+ in equilibrium Fe3+) show enhanced sensitivity to radiation damage due to the metal-catalyzed induction of lipid peroxidation by ionizing radiation. Disruption of secretory granules would be expected to release lytic enzymes into the cell sap, resulting in autolysis. This hypothesis is supported by the findings that atropine--which increases the number of granulated serous cells--enhances radiosensitivity, while noradrenaline and phenylephrine--which cause degranulation of serous cells--decrease radiosensitivity.

Animals↗

PubMed1997

The effect of paclitaxel on the radiosensitivity of gynecological tumor cells.

BACKGROUND: Paclitaxel, a natural product from Taxus brevifolia, is a microtubule stabilizing agent, which has been shown to block different cells in the G2/M phase of the cell cycle and consequently, to modulate their radioresponsiveness. Our aim was to test the cytotoxic and radiosensitizing potential of paclitaxel, with respect to different gynecological tumors with varying radiosensitivities. MATERIAL AND METHOD: We performed clonogenic assays and flow cytometry on 2 cell lines, MCF-7 (breast) and CaSki (cervix) cells, and on 2 primary ovarian tumor samples (OC-I and OC-II). The cells were irradiated with 200 kV X-rays, radiation doses of up to 8 Gy were applied either as single doses or in 2 Gy fractions. Paclitaxel concentrations varied from 0.07 to 700 nM, incubation times varied from 3 to 120 h. RESULTS: Paclitaxel alone changed the cell cycle distribution of the cells tested and was cytotoxic in a time and concentration dependent manner. When combined with radiation, most schedules resulted in additive effects of the combined treatments. However, for MCF-7 cells, when 7 nM paclitaxel, applied 24 h before irradiation, were combined with fractionated irradiation a supra-additive effect with a SER of 1.2 was found. For CaSki cells, under comparable conditions the SER was 1.13 but the effects were not statistically significant. CONCLUSION: Under specific conditions, paclitaxel exerted a weak radiosensitizing effect on breast and cervical carcinoma cells. A therapeutic gain may be possible on the basis of an optimal paclitaxel/radiation scheduling.

Antineoplastic Agents, Phytogenic↗

PubMed2004

Radiation response in vitro of fibroblasts from a fanconi anemia patient with marked clinical radiosensitivity.

BACKGROUND: . Fanconi anemia (FA) is an autosomal recessive chromosome instability disorder characterized by progressive pancytopenia and cancer susceptibility. The risks of radiation therapy in FA patients who have cancer remain to be investigated. Recently, Marcou et al. (2001) reported a case of severe clinical radiosensitivity in a female FA patient with a tonsillar squamous cell carcinoma treated by radiotherapy. By contrast, her in vitro irradiated skin fibroblasts revealed nearly normal radiosensitivity as determined by the colony survival assay. MATERIAL AND METHODS: . In view of this discrepancy, the radiation response of this particular FA fibroblast strain (designated 425BR) was further analyzed in the present study by means of the alkaline single-cell gel electrophoresis (Comet) assay, and also by the cytochalasin-blocked micronuclei (MN) test. In addition, the expression levels of DNA repair proteins, hMre11, Rad50, and Rad51, were investigated using Western blot and foci immunofluorescence staining. RESULTS: . The Comet assay revealed that the initial DNA fragmentation in irradiated FA cells was two times higher and the DNA rejoining process was three times slower than that in control (1BR3) fibroblasts. Moreover, although the baseline level of MNs was lower in FA cells than in controls, the FA fibroblasts were more prone (about two times) to MN production than control cells when irradiated with 2-4 Gy. Western blot analysis of the DNA repair proteins (hMre11, Rad50, and Rad51) did not reveal any abnormalities in protein expression levels or their migration patterns in the fibroblasts derived from an FA patient either before or after irradiation. At the same time, in vitro irradiated cells from the FA patient exhibited a significantly reduced number of nuclei with focally concentrated DNA repair Rad51 protein than in control cells. CONCLUSION: . The increased DNA damage and MN induction in irradiated FA fibroblasts, and the reduction of the formation of DNA repair foci containing Rad51 suggest a possible link to the profound clinical radiosensitivity reported earlier for this FA patient. The findings on this particular FA cell strain presented in the study point toward the difficulties involved in the prediction of the radiation response of cell lines and tumors based solely on the colony survival test.

Adult↗

PubMed2005

Radiosensitivity of tumor cell lines after pretreatment with the EGFR tyrosine kinase inhibitor ZD1839 (Iressa).

BACKGROUND AND PURPOSE: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor ZD1839 (Iressa) reduces survival and augments radiation response of certain tumor cells. The aim of this study was to identify cellular events that are associated with the modulation of radiosensitivity by ZD1839. MATERIAL AND METHODS: Three tumor cell lines (A549, H596, FaDu) were exposed to ionizing radiation, treatment with ZD1839, and combined treatment. Clonogenic cell survival was determined by colony assays, EGFR and transforming growth factor-(TGF-)alpha expression by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), cell cycle distribution and apoptosis by flow cytometry. RESULTS: In A549 and H596 cells ZD1839 had little effect on clonogenic growth, but survival curves revealed a radiosensitizing effect of 5 microM ZD1839 on A549 cells. Both cell lines expressed moderate amounts of EGFR mRNA and very low levels of TGF-alpha mRNA. FaDu cells expressed relatively high amounts of EGFR and TGF-alpha transcripts and showed marked inhibition of clonogenic growth, reduction of S-phase cells, and induction of apoptosis after treatment with 1 microM ZD1839 and combined treatment. Surprisingly, the subpopulation of FaDu cells surviving ZD1839 pretreatment was more radioresistant. Exposure to ZD1839 caused a decrease in EGFR mRNA expression in A549 cells, no change in H596, and even an increase in FaDu cells. CONCLUSION: The sensitivity to ZD1839 correlated with the EGFR expression level, an inhibition of cell proliferation, and induction of apoptosis in the cell lines analyzed. A radiosensitizing effect of ZD1839 was associated with downregulation of EGFR mRNA expression.

Adenocarcinoma↗

PubMed2005

Antiproliferation and radiosensitization of caffeic acid phenethyl ester on human medulloblastoma cells.

PURPOSE: To investigate antiproliferative and radiosensitizing effects of caffeic acid phenethyl ester (CAPE) on medulloblastoma (MB) Daoy cells. METHODS AND MATERIALS: Daoy cells were treated with CAPE in different concentrations and assessed for cell viability, apoptosis, cell cycles, cyclin B1 expressions, radiosensitization and chemosensitization. Human astroglia SVGp12 cells were treated with CAPE to present the possible protection or complication effects in normal tissues. RESULTS: CAPE inhibited the growth of Daoy cells in a time- and concentration-dependent manner in MTT and Trypan blue exclusion assays. Flow cytometry revealed that CAPE significantly decreased G2/M fraction, and increased the S phase fraction. Western blot demonstrated a down-regulated cyclin B1 protein expression. Pretreatment with CAPE markedly decreased the viability of irradiated Daoy cells. The sensitizer enhancement ratios (SERs) were increased in CAPE-treated Daoy cells. CAPE in doxorubicin and cisplatin did not show chemosensitizing effect. CONCLUSIONS: These findings demonstrate the antiproliferative and radiosensitizing effects of CAPE for Daoy cells, which might bring improvement to the treatment of MB. For clinical application, in vivo models are expected.

Antibiotics, Antineoplastic↗

PubMed1999

Radiosensitization of advanced squamous cell carcinoma of the head and neck with cisplatin during concomitant radiation therapy.

Treatment regimens for advanced squamous cell carcinoma of the head and neck require both attention to local tumor burden as well as contingencies for control of disseminated disease. Relatively new protocols utilizing cisplatin for radiosensitization of tumor cells during concomitant radiotherapy have shown progress in providing effective tumor control. Cisplatin as a chemotherapeutic agent induces DNA changes in malignant cells that may be mutagenic or lethal. Additionally, when used concurrently with radiation therapy, cisplatin acts as a radiosensitizer, increasing damage to malignant nuclear DNA to enhance the anti-neoplastic capability of radiotherapy. The mechanisms by which this radiosensitization occurs remain controversial, although one leading theory involves cisplatin's ability to inhibit sublethal damage repair in radiated tumor cells. Recent investigations utilizing cisplatin with concurrent radiation for treatment of advanced squamous cell carcinomas of the head and neck are reviewed. The variations in protocols presented include route of administration, dosing, scheduling, timing with surgery, and combination therapy with 5-fluorouracil and radiation. Higher response rates, prolonged mean survival, increased survival rates, longer local recurrence-free survival rates, and considerable organ preservation with the use of concurrent cisplatin and radiation have been demonstrated by these studies. Further investigation of concurrent cisplatin and radiotherapy in patients with advanced disease is justified.

Carcinoma, Squamous Cell↗

PubMed2001

The relationship between the RBE of alpha particles and the radiosensitivity of different mutations of Chinese hamster cells.

The RBE of alpha-particles in different mutations of Chinese hamster cells was determined with the aim of identifying differences in the sensitivity to x-ray and alpha-particle-induced DNA damage. Two parental lines of Chinese hamster cells and four radiosensitive mutants were irradiated with different single doses of x-rays and alpha-particles and clonogenic cell survival was determined. Radiosensitivity to x-rays varied by a factor of 5 between the cell strains whereas sensitivity to alpha-particle irradiation was almost identical among all strains. The RBE is only determined by the sensitivity of the cells towards x-rays. Since cells with different defects of repair or cell cycle control have different radiosensitivities, we conclude that the effects of x-ray irradiation and the RBE are mostly determined by the activity of repair processes.

Alpha Particles↗

PubMed2001

Recombinant human erythropoietin increases the radiosensitivity of xenografted human tumours in anaemic nude mice.

PURPOSE: The effect of recombinant human erythropoietin (Epo) on the radiosensitivity of human tumour xenografts growing in anaemic nude mice was studied. METHODS AND MATERIALS: Anaemia was induced by total body irradiation (TBI) of mice prior to tumour transplantation. The development of anaemia was prevented by Epo (1000 U/kg s.c.) given 3 times weekly starting 2 weeks prior to TBI (5 Gy). Epo treatment did not influence the growth rate of the tumours, which were transplanted into the subcutis of the hind leg of mice. Thirteen days after TBI (tumour volume of approx. 40 mm3), a single-dose irradiation (12 Gy) of the tumour was performed resulting in a growth delay with subsequent regrowth of the tumours. RESULTS: In Epo-treated animals the tumour growth delay was significantly longer compared to anaemic mice. However, the radiosensitivity of tumours in non-anaemic animals' (non-Epo-treated) tumours could not fully be restored. CONCLUSION: These data give evidence for restored radiosensitivity after correction of anaemia with Epo.

Anemia↗