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Results for “Radiosensitivity”

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At least 613 records · Page 34Linked to original sources

PubMed2005

Antitumor effects and radiosensitization of cytosine deaminase and thymidine kinase fusion suicide gene on colorectal carcinoma cells.

AIM: To investigate the killing effect and radiosensitization of double suicide gene mediated by adenovirus on colorectal carcinoma cells. METHODS: Colorectal carcinoma cell line SW480 was transfected with adenovirus expression vector containing cytosine deaminase (CD) and thymidine kinase (TK) fusion gene. The expression of CD-TK fusion gene was detected by reverse transcriptase-polymerase chain reaction. The toxic effect of ganciclovir (GCV) and 5-fluorocytosine (5-FC) on infected cells was determined by MTT assay. The radiosensitization of double suicide gene was evaluated by clonogenic assay. RESULTS: After prodrugs were used, the survival rate of colorectal carcinoma cells was markedly decreased. When GCV and 5-FC were used in combination, the cytotoxicity and bystander effect were markedly superior to a single prodrug (chi2 = 30.371, P<0.01). Both GCV and 5-FC could sensitize colorectal carcinoma cells to the toxic effect of radiation, and greater radiosensitization was achieved when both prodrug were used in combination. CONCLUSION: CD-TK double suicide gene can kill and radiosensitize colorectal carcinoma cells.

Adenoviridae↗

PubMed2005

Radiosensitivity of human colon cancer cell enhanced by immunoliposomal docetaxel.

AIM: To enhance the radiosensitivity of human colon cancer cells by docetaxel. METHODS: Immunoliposomal docetaxel was prepared by coupling monoclonal antibody against carcinoembryonic antigen to cyanuric chloride at the PEG terminus of liposome. LoVo adenocarcinoma cell line was treated with immunoliposomal docetaxel or/and irradiation. MTT colorimetric assay was used to estimate cytotoxicity of immunoliposomal docetaxel and radiotoxicity. Cell cycle redistribution and apoptosis were determined with flow cytometry. Survivin expression in LoVo cells was verified by immunohistochemistry. D801 morphologic analysis system was used to semi-quantify immunohistochemical staining of survivin. RESULTS: Cytotoxicity was induced by immunoliposomal docetaxel alone in a dose-dependent manner. Immunoli-posomal docetaxel yielded a cytotoxicity effect at a low dose of 2 nmol/L. With a single dose irradiation, the relative surviving fraction of LoVo cells showed a dose-dependent response, but there were no significant changes as radiation delivered from 4 to 8 Gy. Compared with liposomal docetaxel or single dose irradiation, strongly radiopotentiating effects of immunoliposomal docetaxel on LoVo cells were observed. A low dose of immunoliposomal docetaxel could yield sufficient radiosensitivity. Immunoliposomal docetaxel were achieved both specificity of the conjugated antibody and drug radiosensitization. Combined with radiation, immunoliposomal docetaxel significantly increased the percentage of G(2)/M cells and induced apoptosis, but significantly decreased the percentage of cells in G(2)/G(1) and S phase by comparison with liposomal docetaxel. Immunohistochemical analysis showed that the brown stained survivin was mainly in cytoplasm of LoVo cells. Semi-quantitative analysis of the survivin immunostaining showed that the expression of survivin in LoVo cells under irradiation with immunoliposomal docetaxel was significantly decreased. CONCLUSION: Immunoliposomal docetaxel is strongly effective for target radiosensitation in LoVo colon carcinoma cells, and may offer the potential to improve local radiotherapy.

Cell Line, Tumor↗

PubMed2005

Cell cycle and radiosensitivity of progeny of irradiated primary cultured human hepatocarcinoma cells.

AIM: To evaluate the change of growth characteristics and radiosensitivity of irradiated primary cultured human hepatocarcinoma cells. METHODS: All tumor tissue samples were obtained from 39 hepatocarcinoma patients with a mean age of 49.6 years (range 22-76 years). We divided the samples into irradiated group and non-irradiated group and measured their plating efficiency (PE), population doubling time (PDT), radiosensitivity index SF2 and cell cycle. RESULTS: The PDT of primary culture of hepatocarcinoma cells was 91.0+/-6.6 h, PE was 12.0+/-1.4%, SF2 was 0.41+/-0.05%. The PDT of their irradiated progeny was 124.8+/-5.8 h, PE was 5.0+/-0.7%, SF2 was 0.65+/-0.09%. The primary cultured human hepatocarcinoma cells showed significant S reduction and G(2) arrest in a dose-dependent manner. The progeny of irradiated primary cultured hepatocarcinoma cells grew more slowly and its radiosensitivity increased. CONCLUSION: The progeny of irradiated primary cultured human hepatocarcinoma cells grows more slowly and its radiosensitivity increases.

Adult↗

PubMed1999

Lung metastasis suppression of the bifunctional new radiosensitizer KIN-806.

KIN-806 is one of the newly developed 2-nitroimidazole derivative hypoxic cell radiosensitizers. The tumor growth control and the suppression of lung metastasis induced by KIN-806 were evaluated. Female C3H/He mice and SCCVII tumor cells were used. 30 Gy or 40 Gy was delivered as local irradiation. 0.2 g/kg or 0.4 g/kg KIN-806 was administered 30 min before this treatment to the KIN-806 administered groups. The enhancement ratio of KIN-806 evaluated using the growth delay method was 1.8. KIN-806 showed an excellent effect as a radiosensitizer. Furthermore, KIN-806 suppressed lung metastasis regardless of radiation, and the control of the metastatic lung nodules did not depend on the irradiation dose but rather on the KIN-806 dose (0.2 g/kg < 0.4 g/kg). KIN-806 is a promising bifunctional radiosensitizer which promotes anti-tumor activity in addition to having a radiosensitizing effect.

Animals↗

PubMedDate not supplied

Radiosensitization in sarcoma cell lines with a p53 missense mutation correlates with prevention of irradiation G2/M arrest but not with induction of apoptosis.

We analysed the effects of caffeine and taxol on the radiobiological behaviour of two human sarcoma cell lines (RD, SK-LMS-1) each with a p53 missense mutation. Treatment with 2 mM caffeine resulted in an inhibition of the irradiation induced G2/M arrest in both cell lines. This effect was coupled with a radiosensitization in cell line SK-LMS-1 after an irradiation with 6 Gy (enhancement factor of 5.0). However, the effect of radiosensitization was not correlated with an induction of apoptosis. Incubation with 20 nM taxol increased the irradiation induced apoptosis almost 3-fold in cell line SK-LMS-1, but not in cell line RD. However, taxol had no effect on the irradiation induced G2/M arrest or radiosensitivity in either cell line. The results support the hypothesis that the prevention of irradiation induced G2/M arrest but not the induction of apoptosis plays a critical role in determining radiosensitivity in sarcoma cell lines with p53 mutations.

Apoptosis↗

PubMed2004

Radiosensitization of Escherichia coli and Salmonella Typhi in ground beef.

The radiosensitization of two pathogenic bacteria, Escherichia coli and Salmonella Typhi, was evaluated in the presence of thyme and its principal essential oil constituents (carvacrol and thymol) in ground beef. Ground beef was inoculated with E. coli or Salmonella Typhi (10(5) CFU/g), and each compound was added separately at various concentrations (0 to 3.5%, wt/wt). The antimicrobial potential of carvacrol, thymol, and thyme was evaluated in unirradiated meat by determining the MIC in percentage (wt/wt) after 24 h of storage at 4 +/- 1 degree C. Results showed a MIC of 0.88 +/- 0.12%, 1.14 +/- 0.05%, and 2.33 +/- 0.32% for E. coli in the presence of carvacrol, thymol, and thyme, respectively. MICs of 1.15 +/- 0.02%, 1.60 +/- 0.01%, and 2.75 +/- 0.17% were observed for Salmonella Typhi in the presence of the same compounds, respectively. The best antimicrobial compound (i.e., carvacrol) was selected and added to the sterilized ground beef along with ascorbic acid (0.5%, wt/wt) and tetrasodium pyrophosphate (0.1%, wt/wt). Meat samples (10 g) were packed in air and then irradiated in a 60Co irradiator at doses of 0 to 0.7 kGy for the determination of E. coli radiation D10 and 0 to 2.25 kGy for the determination of Salmonella Typhi radiation D10. Addition of carvacrol increased the relative sensitivity of both bacteria 2.2 times. The radiation D10 was reduced from 0.126 +/- 0.0039 to 0.057 +/- 0.0015 kGy for E. coli and from 0.519 +/- 0.0308 to 0.235 +/- 0.0158 kGy for Salmonella Typhi. The addition of tetrasodium pyrophosphate did not affect significantly (P > 0.05) the radiosensitization of either bacterium. However, the presence of ascorbic acid in the media reduced significantly (P < or = 0.05) the radiosensitivity of both bacteria. An additive effect of carvacrol addition and packaging under modified atmosphere conditions (60% O2-30% CO2-10% N2) was also observed on bacterial radiosensitization at 4 degrees C. Compared with the control packed under air, modified atmosphere packaging conditions in the presence of carvacrol and tetrasodium pyrophosphate improved the relative sensitivity of E. coli by 2.7 times and Salmonella Typhi by 9.9 times.

Animals↗

PubMed2003

Radiosensitivity of rat mammary tumors correlates with early vessel changes assessed by power Doppler sonography.

OBJECTIVE: To investigate the changes occurring in the vascularization of tumors during irradiation, we used a model of autochthonous mammary tumors in rats and assessed early vascular changes after irradiation by power Doppler sonography. METHODS: Mammary tumors were induced in 24 female Sprague Dawley rats by a single subcutaneous injection of N-nitroso N-methyl urea. After tumor areas reached 1 cm2, the animals received a single fraction of 18-Gy radiation or intraperitoneal saline injection. Power Doppler sonographic quantification of detected vessels was performed 1 day before irradiation and 7 days after the use of a power Doppler index of 5 different tumor imaging planes. Final tumor shrinkage was compared with early changes in the power Doppler index. Not all tumors regressed in a similar fashion. Radiosensitive tumors were defined as tumors with a greater than 50% decrease in baseline area 28 days after irradiation, whereas radioresistant tumors were tumors with a less than 50% decrease in baseline area. Statistical analysis was performed by the Mann-Whitney U test. RESULTS: Tumor area changes were similar in radioresistant and radiosensitive tumors 7 days after irradiation (-41% and -35%, respectively; P > .05, not significant), whereas reduction in the power Doppler index was significantly greater in radiosensitive tumors (mean value, -63%) than in radioresistant tumors (mean value, -12%) (P = .001). Late tumor regrowth was correlated with day 7 power Doppler index changes (P = .009). A 40% reduction in the power Doppler index at day 7 distinguished 8 of 9 radiosensitive tumors and 8 of 9 radioresistant tumors (P = .003). CONCLUSIONS: This study suggests that early changes in tumor perfusion as assessed by power Doppler sonography after tumor irradiation may precede the long-term tumor regression.

Animals↗

PubMed1999

Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine.

Caffeine exposure sensitizes tumor cells to ionizing radiation and other genotoxic agents. The radiosensitizing effects of caffeine are associated with the disruption of multiple DNA damage-responsive cell cycle checkpoints. The similarity of these checkpoint defects to those seen in ataxia-telangiectasia (A-T) suggested that caffeine might inhibit one or more components in an A-T mutated (ATM)-dependent checkpoint pathway in DNA-damaged cells. We now show that caffeine inhibits the catalytic activity of both ATM and the related kinase, ATM and Rad3-related (ATR), at drug concentrations similar to those that induce radiosensitization. Moreover, like ATM-deficient cells, caffeine-treated A549 lung carcinoma cells irradiated in G2 fail to arrest progression into mitosis, and S-phase-irradiated cells exhibit radioresistant DNA synthesis. Similar concentrations of caffeine also inhibit gamma- and UV radiation-induced phosphorylation of p53 on Ser15, a modification that may be directly mediated by the ATM and ATR kinases. DNA-dependent protein kinase, another ATM-related protein involved in DNA damage repair, was resistant to the inhibitory effects of caffeine. Likewise, the catalytic activity of the G2 checkpoint kinase, hChk1, was only marginally suppressed by caffeine but was inhibited potently by the structurally distinct radiosensitizer, UCN-01. These data suggest that the radiosensitizing effects of caffeine are related to inhibition of the protein kinase activities of ATM and ATR and that both proteins are relevant targets for the development of novel anticancer agents.

Ataxia Telangiectasia Mutated Proteins↗

PubMed1999

Radiosensitization of human tumor cell lines induced by the adenovirus-mediated expression of an anti-Ras single-chain antibody fragment.

The expression of activated ras genes has been implicated as a contributing factor to the radioresistance of tumor cells. As a strategy for compromising Ras protein activity and potentially enhancing the radiosensitivity of tumor cells, we have investigated the application of the AV1Y28 adenovirus, which expresses a single-chain antibody fragment directed against p21 Ras proteins. The ability of AV1Y28 transduction to modulate radioresponse was investigated using four human tumor cell lines--U251 glioblastoma, MIA PaCa-2 pancreatic carcinoma, and the colon carcinomas SW620 and HT29. Cultures were exposed to sufficient levels of AV1Y28 to transduce more than 90% of the cells; 24 h later, cultures were exposed to ionizing radiation, and clonogenic cell survival was determined. Tumor cell survival was reduced by 40-50% when the tumor cell lines were exposed to AV1Y28 only. In addition, for each tumor cell line, AV1Y28 exposure enhanced the level of radiation-induced cell killing. Dose enhancement factors at a surviving fraction of 0.1 ranged from 1.3 to 1.5. Furthermore, for each of the cell lines, the surviving fraction at 2 Gy was significantly reduced by AV1Y28 exposure. In contrast to the results seen in tumor cells, the radiosensitivity of a normal human fibroblast cell line was not affected by AV1Y28. These data indicate that this anti-Ras adenovirus enhances the radiosensitivity of tumor cells but does not affect the radiosensitivity of normal cells.

Adenoviridae↗

PubMed1999

Ataxia telangiectasia mutated deficiency affects astrocyte growth but not radiosensitivity.

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 Atm-/- mice have cell cycle and growth defects and are generally considered radiosensitive. However, it has been shown recently that cell populations in the Atm-/- central nervous system are radioresistant. To define specific IR sensitivities of neural populations, we analyzed Atm-/- astrocytes. Here we show that Atm-/- astrocytes exhibit premature senescence, express constitutively high levels of p21, and have impaired p53 stabilization. However, in contrast to radiosensitive Atm-/- fibroblasts and radioresistant Atm-/- neurons, survival of Atm-/- astrocytes after IR was similar to wild-type astrocytes. Additionally, p53-null astrocytes, but not fibroblasts, were moderately more radioresistant than their wild-type counterparts, suggesting that the deficit in p53 stabilization observed in Atm-null cells is not a measure of radiation susceptibility. Thus, in astrocytes, the function of Atm in cellular growth and radiosensitivity is distinct. These data may have implications for ATM disruption strategies as a radiosensitizing treatment for brain tumors.

Animals↗

PubMed2000

Selective radiosensitization of drug-resistant MutS homologue-2 (MSH2) mismatch repair-deficient cells by halogenated thymidine (dThd) analogues: Msh2 mediates dThd analogue DNA levels and the differential cytotoxicity and cell cycle effects of the dThd analogues and 6-thioguanine.

Mismatch repair (MMR) deficiency, which underlies hereditary nonpolyposis colorectal cancer, has recently been linked to a number of sporadic human cancers as well. Deficiency in this repair process renders cells resistant to many clinically active chemotherapy agents. As a result, it is of relevance to find an agent that selectively targets MMR-deficient cells. We have recently shown that the halogenated thymidine (dThd) analogues iododeoxyuridine (IdUrd) and bromodeoxyuridine (BrdUrd) selectively target MutL homologue-1 (MLH1)-deficient human cancer cells for radiosensitization. The levels of IdUrd and BrdUrd in cellular DNA directly correlate with the ability of these analogues to increase the sensitivity of cells and tissues to ionizing radiation, and data from our laboratory have demonstrated that MLH1-mediated MMR status impacts dThd analogue DNA levels, and consequently, analogue-induced radiosensitization. Here, we have extended these studies and show that, both in human and murine cells, MutS homologue-2 (MSH2) is also involved in processing dThd analogues in DNA. Using both E1A-transformed Msh2+/+ and Msh2-/- murine embryonic stem (ES)-derived cells (throughout this report we use Msh2+/+ and Msh2-/- to refer to murine ES-derived cell lines that are wild type or mutant, respectively, for the murine Msh2 gene) and human endometrial cancer cells differing in MSH2 status, we see the classic cytotoxic response to 6-thioguanine (6-TG) in Msh2+/+ and human HEC59/2-4 (MSH2+) MMR-proficient cells, whereas Msh2-/- cells and human HEC59 (MSH2-/-) cells are tolerant (2-log difference) to this agent. In contrast, there is very little cytotoxicity in Msh2+/+ ES-derived and HEC59/2-4 cells to IdUrd, whereas Msh2-/- and HEC59 cells are more sensitive to IdUrd. High-performance liquid chromatography analysis of IdUrd and BrdUrd levels in DNA suggests that this differential cytotoxicity may be due to lower analogue levels in MSH2+ murine and human tumor cells. The DNA levels of IdUrd and BrdUrd continue to decrease over time in Msh2+/+ cells following incubation in drug-free medium, whereas they remain high in Msh2-/- cells. This trend was also found in MSH2-deficient human endometrial cancer cells (HEC59) when compared with HEC59/2-4 (hMsh2-corrected) cells. As a result of higher analogue levels in DNA, Msh2-/- cells are selectively targeted for radiosensitization by IdUrd. Fluorescence-activated cell-sorting analysis of Msh2+/+ and Msh2-/- cells shows that selective toxicity of the halogenated nucleotide analogues is not correlated with a G2-M cell cycle arrest and apoptosis, as is found for selective killing of Msh2+/+ cells by 6-TG. Together, these data demonstrate MSH2 involvement in the processing of IdUrd and BrdUrd in DNA, as well as the differential cytotoxicity and cell cycle effects of the halogenated dThd analogues compared with 6-TG. Therefore, IdUrd and BrdUrd may be used clinically to selectively target both MLH1- and MSH2-deficient, drug-resistant cells for radiosensitization.

Adenovirus E1A Proteins↗

PubMed2001

Differential p53-dependent mechanism of radiosensitization in vitro and in vivo by the protein kinase C-specific inhibitor PKC412.

The cellular response to ionizing radiation is governed by the DNA-damage recognition process but is also modulated by cytoplasmic signal transduction cascades that are part of the cellular stress response. Growth-promoting protein kinase C activity antagonizes irradiation-induced cell death, and, therefore, protein kinase C inhibitors might be potent radiosensitizers. The antiproliferative and radiosensitizing effect of the novel N-benzoylated staurosporine analogue PKC412 was tested in vitro against genetically defined p53-wild type (+/+) and p53-deficient (-/-) murine fibrosarcoma cells and in vivo against radioresistant p53-/- murine fibrosarcoma and human colon adenocarcinoma tumor xenograft (SW480, p53-mutated). PKC412 sensitized both p53+/+ and p53-/- tumor cells in vitro and in vivo for treatment with ionizing radiation but with a different mechanism of radiosensitization depending on the p53 status. In p53+/+, cells combined treatment with PKC412 and ionizing radiation drastically induced apoptotic cell death, whereas no apoptosis induction could be observed in p53-deficient cells in vitro and in histological tumor sections. Combined treatment resulted in an increased G2 cell cycle distribution in p53-/- cells at PKC412 concentrations that did not alter cell cycle distribution when applied alone. In vivo, a minimal treatment regimen during 4 consecutive days of PKC412 (4 x 100 mg/kg) in combination with ionizing radiation (4 x 3 Gy) exerted a substantial tumor growth delay for both p53-disfunctional tumor xenografts and showed that the clinically relevant protein kinase C inhibitor PKC412 is a promising new radiosensitizer with a potentially broad therapeutic window.

Animals↗

PubMed2000

Radiosensitivity of tumor cells. Oncogenes and apoptosis.

The success of treatment of cancer patients by radiotherapy largely depends on tumor radiosensitivity. Several molecular factors that determine the sensitivity of tumor cells to ionizing radiation have been identified during the last couple of years. Some of these factors are known as oncogenes and tumor suppressor genes. This review focuses on the influence of some of these molecular factors on a major determinant of radiosensitivity: i.e. programmed cell death or apoptosis. The crucial molecular step in ionizing radiation-induced apoptosis is the release of mitochondrial cytochrome c into the cell's cytosol. The ways the tumor suppressor protein p53, as well as the oncogenes ras and raf, c-myc and Bcl-2 can influence this process at different stages are presented. As will be discussed, the result of activation of an oncoprotein on tumor radiosensitivity depends on its mechanism of action and on the presence of other (oncogenic) factors, since complex interactions among many molecular factors determine the delicate balance between cell proliferation and cell death. The ongoing identification and characterization of factors influencing apoptosis will eventually make it possible to predict tumor radiosensitivity and thereby improve cancer treatment.

Apoptosis↗

PubMed2001

Indomethacin-induced radiosensitization and inhibition of ionizing radiation-induced NF-kappaB activation in HeLa cells occur via a mechanism involving p38 MAP kinase.

Although ionizing radiation (IR) activates multiple cellular factors that vary depending on dose and tissue specificity, the activation of NF-kappaB appears to be a well-conserved response in tumor cells exposed to IR. Recently, it also has been demonstrated that nonsteroidal anti-inflammatory agents inhibit tumor necrosis factor and interleukin-1-induced NF-kappaB activation and act as radiosensitizing agents. These observations reinforce the growing notion that NF-kappaB may be a protective cellular factor responding to the cytotoxicity of IR and other damaging stimuli. As such, we addressed the idea and mechanism that NF-kappaB is a downstream target of the nonsteroidal anti-inflammatory agent indomethacin and is involved in the process of radiosensitization. In this study, we report that indomethacin inhibited IR-induced activation of NF-kappaB and sensitized HeLa cells to IR-induced cytotoxicity at similar concentrations. Pretreatment of HeLa cells with SB 203580, a pyridinyl imidazole compound that specifically inhibits p38 mitogen-activated protein kinase (MAPK), abrogated the ability of indomethacin to inhibit IR-induced activation of NF-kappaB and diminished the indomethacin radiosensitizing effect. In addition, the transient genetic activation of p38(MAPK) inhibited IR induction of NF-kappaB gene expression in the absence of indomethacin. Finally, permanently transfected cell lines genetically unable to activate NF-kappaB, because of expression of a dominant negative I-kappaBalpha gene, demonstrated increased sensitivity to IR-induced cytotoxicity. Taken together, these results suggest that p38 MAPK is a target involved in indomethacin-induced radiosensitization and that NF-kappaB may be one downstream target in this process.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2003

Flavopiridol, a cyclin-dependent kinase inhibitor, enhances radiosensitivity of ovarian carcinoma cells.

Flavopiridol, a cyclin-dependent kinase (cdk) inhibitor, can cause cell cycle arrest, induce apoptosis in cancer cells, and inhibit tumor cell growth in vivo. The present study investigated the in vitro radiosensitizing effect of flavopiridol and the underlying molecular mechanisms in a murine ovarian cancer cell line, OCA-I. Flavopiridol inhibited cell growth in a dose-dependent manner and enhanced cell radiosensitivity assessed by the clonogenic cell survival assay. A flavopiridol dose of 300 nM, given for 1 day, enhanced radiosensitivity by a factor of 2.1. Clonogenic cell survival after split-dose radiation showed that flavopiridol inhibited repair from radiation damage. In addition, flavopiridol treatment (300 nM, 1 day) resulted in decreased levels of Ku70 and Ku86 proteins that play a role in DNA repair processes, suggesting that DNA repair processes may have been disrupted by this agent. Flow cytometry analysis showed that flavopiridol (300 nM, 1 day) accumulated the cells in G(1) and G(2) phases, with a significant reduction in the S phase component. This cell cycle redistribution is likely another mechanism underlying flavopiridol-induced cell radiosensitivity. Flavopiridol down-regulated cyclin D1 and cyclin E protein levels and also inhibited phosphorylation of retinoblastoma protein, which is inconsistent with the observed cell cycle arrest. Among the cdks tested, cdk-9, the catalytic subunit of positive transcription elongation factor b, was significantly down-regulated by flavopiridol, suggesting that flavopiridol may modulate cellular transcription processes. Furthermore, flavopiridol on its own induced apoptosis in the OCA-I cells, whereas in combination with radiation, exerted no additional increase in apoptosis. Taken together, our data show that flavopiridol strongly augmented the response of ovarian carcinoma cells to radiation and that the underlying mechanisms included inhibition of sublethal DNA damage repair and cell cycle redistribution. At the molecular level, transcriptional regulation by flavopiridol may have been involved.

Animals↗

PubMedDate not supplied

Interaction of radiation and etoposide on two cell lines with different radiosensitivities in vitro.

PURPOSE: To investigate the differences between two rat yolk sac tumor cell lines with different radiosensitivities in etoposide sensitivity and in the sensitizing effect of etoposide in combination with irradiation. MATERIALS AND METHODS: NMT-1 is a parent radiosensitive cell line and NMT-1R is a variant radioresistant cell line. The effects were assessed by clonogenic assay. Apoptosis was evaluated by DNA fragmentation to investigate the mechanism of cell death. RESULTS: Etoposide potentiation of radiation sensitivity was manifested by elimination of the initial shoulder of the cell survival curve in radioresistant NMT-1R cells. However, there was no enhancement effect in radiosensitive NMT-1 cells. The incidence of apoptosis was elevated in NMT-1R cells treated with etoposide and radiation. CONCLUSION: Etoposide had a supra-additive effect in combination with irradiation for radioresistant NMT-1R cells due to the induction of apoptosis. However, a suppra-additive effect was not seen in radiosensitive NMT-1 cells.

Animals↗

PubMed1992

[Synthesis and radiosensitizing activity of benzimidazoles].

In search for effective radiosensitizer with low neurotoxicity, benzimidazole compounds were synthesized. Reaction of 2-nitrobenzimidazole with ethyl chloroformate yielded ethyl alpha-(2-nitrobenzimidazolyl-1)-formate(1) or ethyl alpha-(2-hydroxybenzimidazolyl-1)-formate(2), depending upon the solvents used. Reaction of 2-nitrobenzimidazole with 1,2-epoxy-3-chloropropane gave a cyclized compound which was confirmed to be benzimidazo(1,2b)-5'-chloromethyl-oxazolidine(3). In attempt to increase hydrophilicity, 1-substituted 2(3'-pyridyl)-5-nitrobenzimidazoles were prepared by reaction of 2-(3'-pyridyl)-5(6)-nitrobenzimidazole(4) with alkyl epoxides or ethyl chloroacetate. Some of the compounds synthesized were tested for radiosensitizing activity in Ehrlich ascites carcinoma-bearing mice. Preliminary results showed that some compounds have radiosensitizing activity. The radiosensitizing enhancement ratio (SER) of compounds 3, 5 and 6 were found to be 1.50, 1.52 and 1.65 respectively.

Animals↗

PubMed2003

[Expression of ATM protein in nasopharyngeal carcinoma cell lines with different radiosensitivity].

BACKGROUND & OBJECTIVE: It has been reported that ataxia- telangiectasia mutant(ATM) protein is closely correlated with cellular radiosensitivity in several malignant tumors. This study was designed to determine the expression of ATM protein in two nasopharyngeal carcinoma (NPC) cell lines with different radiosensitivity. METHODS: Two NPC cell lines, CNE1 and CNE2, with different radiosensitivity were established. The localization and quantity of ATM protein were analyzed by fluorescence immunohistochemical method and laser scanning confocal microscope(LSCM). RESULTS: ATM protein was located in both karyon and cytoplasm, especially strongly expressed in karyon. The intense fluorescence of ATM protein was stronger in karyon of CNE1 than that in CNE2. CONCLUSION: The expression levels of ATM protein differ in CNE1 and CNE2. The variance may be a potential factor, which links with their different radiosensitivity.

Ataxia Telangiectasia Mutated Proteins↗