共查询到20条相似文献,搜索用时 15 毫秒
1.
J H Schwach?fer R P Crooijmans H Hoogenhout H B Kal R Q Schaapveld J Wessels 《Strahlentherapie und Onkologie》1991,167(1):35-40
We studied the relationship between the repair of radiation induced DNA strand breaks and cellular repair kinetics in two human tumor cell lines, NB-100 (neuroblastoma) and HN-1 (squamous cell carcinoma). Damage was quantified using the fluorometric analysis of DNA unwiding (FADU) for DNA damage, and cell survival was assessed using a clonogenic assay. In plateau phase cells repair of sublethal damage was virtually absent in NB-100 after 4 Gy (recovery ratio 1.0), whereas HN-1 cells did show sublethal damage repair (recovery ratio 1.4). Repair of potentially lethal damage was more pronounced in NB-100 cells (recovery ratio 2.3) than in HN-1 cells (recovery ratio 1.7) after 4 Gy. Graded doses of X-rays induced comparable levels of DNA damage in both tumor cell lines. However, in HN-1 cells more DNA strand breaks were repaired after 4 Gy, leaving about 25% of the initial damage unrepaired, whereas in NB-100 about 50% was unrepaired. This higher fraction of unrepaired DNA damage correlated well with the degree of sublethal damage repair which was lower in NB-100 than in HN-1 cell, but it did not correlate with the repair of potentially lethal damage, which was higher in NB-100 than in HN-1. Since the level of damage remaining post-irradiation may be the critical variable for survival, the FADU technique can contribute in elucidating the relationship between radiosensitivity and DNA damage repair capacity. 相似文献
2.
Oxygen radiosensitisation has been studied at dose rates of 600, 3.37 and 0.89 Gy/h at pO2 levels of 0.001, 0.03, 0.1, 0.3, 1, 3, 10 and 21% in the gas phase. The oxygen enhancement ratio (OER), evaluated at 2% cellular survival, exhibited a decrease with dose rate from a value of 3.2 at the acute dose rate, to 2.4 at the lowest dose rate. This observation results from a decreased dose-rate effect on hypoxic cells, which is attributed to the partial suppression of sublethal damage (SLD) repair under hypoxic conditions. Oxygen radiosensitisation at the acute dose rate agrees with the calculated values based on the oxygen fixation hypothesis. Direct application of the Howard-Flanders and Moore equation to results obtained at low dose rate is not appropriate due to the influence of pO2 on SLD repair which affects radiosensitivity at low dose rate. When cells are irradiated at 3.37 Gy/h under nutrient-deprived condition (i.e. in Hanks balanced salt solution without glucose), low levels of oxygen appear to be more radioprotective than extreme hypoxia. Specifically, cells irradiated with 0.03% and 0.1% O2 are more radioresistant than cells under N2, with enhancement factors of 0.7 and 0.8, respectively. This phenomenon can be understood in terms of the ability of moderately hypoxic cells (0.03%-0.1% O2), and inability of anoxic cells, to repair SLD under nutrient deprived conditions. Radiosensitisation by these low levels of oxygen is insufficient to offset the difference caused by the disparate SLD repair capabilities. 相似文献
3.
A dose-rate effect is observed between 1 and 10 Gy/min for cultured Chinese hamster V-79 fibroblast cells irradiated under pO2 levels of less than 10 ppm, 100 ppm, 300 ppm and 21%. The dose for a cellular surviving fraction of 0.1% increases by 10-15% as the dose rate is changed from 10 to 1 Gy/min. This observed dose-rate effect is consistent with the repair of sublethal damage taking place during the radiation delivery. A related finding is that acute hypoxia in cell culture does not inhibit sublethal damage repair. 相似文献
4.
Radiation-induced effects on telomerase in gynecological cancer cell lines with different radiosensitivity and repair capacity 总被引:2,自引:0,他引:2
Kurvinen K Rantanen V Syrjänen S Johansson B 《International journal of radiation biology》2006,82(12):859-867
PURPOSE: Telomerase activation in response to irradiation might enhance the radioresistance of cells. Thus, we have investigated radiation-induced effects on telomerase in six gynecological cancer cell lines, with different intrinsic radiosensitivity and capacity for sublethal damage repair (SLDR). MATERIALS AND METHODS: Three endometrial adenocarcinoma (UM-EC-1, UT-EC-2B and UT-EC-3) and three vulvar squamous cell carcinoma (A431, UM-SCV-2 and UM-SCV-7) cell lines were irradiated with doses of 5, 10 and 25 Gy and the effects on telomerase were evaluated at 0.5, 6, 24 and 48 h post-irradiation. Telomerase activity was quantitatively measured by SYBR Green real-time telomeric repeat amplification protocol. RESULTS: The most radioresistant cell line A431 had the strongest stimulatory effects (approximately 2.0 - 2.5-fold) on telomerase activity 24 and 48 h post-irradiation with the highest radiation doses. In contrast to that, telomerase activities in the highly radiosensitive cell line UT-EC-2B remained below the basal level throughout the 48-h period of post-irradiation with the highest doses, and even a decline to approximately 50% of the basal level was found 24 h after exposure. In other cell lines being either moderately or highly radiation resistant, telomerase activity levels in response to irradiation remained mainly at the basal level or gradually increased. CONCLUSIONS: The present findings indicate that there might be a connection between the radiation-induced telomerase response and radiosensitivity. However, no correlation was found between the radiation-induced effects on telomerase and the sublethal damage repair capacity of the cells. 相似文献
5.
The LD50/30 of CD-1 female mice increased from 6.6 Gy to 7.0 Gy when 2.5 mg of dl-alpha-tocopherol was injected immediately post irradiation. Increased survival was associated with increased numbers of hematopoietic colony forming units (CFU). Endogenous spleen colonies were found in greater numbers in the tocopherol-treated mice after irradiation. The vitamin, however, must be injected within five hours following irradiation to have this effect. The increased numbers of CFU in tocopherol-treated mice may be due to a stimulation of recovery or repair processes. Split-dose studies suggest that most repair of sublethal damage in hematopoietic stem cells take place within seven and nine hours following irradiation. Tocopherol injection appears to enhance the recovery manifested in the split-dose assay. There is also evidence that tocopherol-treatment caused an earlier onset of mitotic activity in CFU after irradiation. The increased number of spleen colonies in tocopherol-injected mice is not due to an altered CFU seeding efficiency associated with an altered spleen microenvironment. Tocopherol injection did not affect the shoulder of the stem cell survival curve using exogenous spleen colony assays of bone marrow-derived or spleen-derived hematopoietic stem cells. There appears to be a decrease in Do in the higher dose region (4.3 Gy) of the bone marrow exogenous SCA survival curves for the vehicle-injected and the non-injected groups; however, the tocopherol-injected group showed no evidence of change in radiosensitivity up to the highest dose used (5.0 Gy). Data may be interpreted to suggest that the therapeutic effect of tocopherol may involve repair of hematopoietic stem cell damage in the higher dose range of bone marrow syndrome. 相似文献
6.
Requirements regarding dose rate and exposure time for killing of tumour cells in beta particle radionuclide therapy 总被引:2,自引:2,他引:0
Carlsson J Eriksson V Stenerlöw B Lundqvist H 《European journal of nuclear medicine and molecular imaging》2006,33(10):1185-1195
Purpose The purpose of this study was to identify combinations of dose rate and exposure time that have the potential to provide curative treatment with targeted radionuclide therapy applying low dose rate beta irradiation.Methods Five tumour cell lines, U-373MG and U-118MG gliomas, HT-29 colon carcinoma, A-431 cervical squamous carcinoma and SKBR-3 breast cancer, were used. An experimental model with 105 tumour cells in each sample was irradiated with low dose rate beta particles. The criterion for successful treatment was absence of recovery of cells during a follow-up period of 3 months. The initial dose rates were in the range 0.1–0.8 Gy/h, and the cells were continuously exposed for 1, 3 or 7 days. These combinations covered dose rates and doses achievable in targeted radionuclide therapy.Results Continuous irradiation with dose rates of 0.2–0.3 and 0.4–0.6 Gy/h for 7 and 3 days, respectively, could kill all cells in each tumour cell sample. These treatments gave total radiation doses of 30–40 Gy. However, when exposed for just 24 h with about 0.8 Gy/h, only the SKBR-3 cells were successfully treated; all the other cell types recovered. There were large cell type-dependent variations in the growth delay patterns for the cultures that recovered. The U-118MG cells were most resistant and the U-373MG and SKBR-3 cells most sensitive to the treatments. The HT-29 and A-431 cells were intermediate.Conclusion The results serve as a guideline for the combinations of dose rate and exposure time necessary to kill tumour cells when applying low dose rate beta irradiation. The shift from recovery to “cure” fell within a narrow range of dose rate and exposure time combinations. 相似文献
7.
J H Schwach?fer R P Crooijmans G F Borm J J van Gasteren J Hoogenhout H B Kal 《Strahlentherapie und Onkologie》1990,166(11):753-760
Growth curves of two human tumour cell lines grown as multicellular tumour spheroid (MTS) were used to obtain survival estimates by back-extrapolation after split and single dose irradiation. Neuroblastoma (NB-100) and squamous cell carcinoma (HN-1) single cells from monolayer culture were assessed for repair of sublethal and potentially lethal damage. The extent of repair was calculated on an iso-effect basis. When grown as spheroids squamous cell carcinoma cells showed a higher capacity to repair sublethal damage than neuroblastoma cells. Repair of potentially lethal damage did not contribute to this higher capacity of HN-1 cells, since this cell line was found to be deficient for this type of repair. Using the recovery ratio to estimate the beta-component of the survival curves, it was found that differences in repair capacity were determined by the alpha-component of the equation. Our results show the feasibility of back-extrapolating multicellular tumour spheroid growth curves to obtain survival estimates that can be applied to establish sublethal damage repair capacity. 相似文献
8.
Kaisa Kurvinen Virpi Rantanen Bo Johansson 《International journal of radiation biology》2013,89(12):859-867
Purpose: Telomerase activation in response to irradiation might enhance the radioresistance of cells. Thus, we have investigated radiation-induced effects on telomerase in six gynecological cancer cell lines, with different intrinsic radiosensitivity and capacity for sublethal damage repair (SLDR).Materials and methods: Three endometrial adenocarcinoma (UM-EC-1, UT-EC-2B and UT-EC-3) and three vulvar squamous cell carcinoma (A431, UM-SCV-2 and UM-SCV-7) cell lines were irradiated with doses of 5, 10 and 25 Gy and the effects on telomerase were evaluated at 0.5, 6, 24 and 48 h post-irradiation. Telomerase activity was quantitatively measured by SYBR Green real-time telomeric repeat amplification protocol.Results: The most radioresistant cell line A431 had the strongest stimulatory effects (~2.0 – 2.5-fold) on telomerase activity 24 and 48 h post-irradiation with the highest radiation doses. In contrast to that, telomerase activities in the highly radiosensitive cell line UT-EC-2B remained below the basal level throughout the 48-h period of post-irradiation with the highest doses, and even a decline to ~50% of the basal level was found 24 h after exposure. In other cell lines being either moderately or highly radiation resistant, telomerase activity levels in response to irradiation remained mainly at the basal level or gradually increased.Conclusions: The present findings indicate that there might be a connection between the radiation-induced telomerase response and radiosensitivity. However, no correlation was found between the radiation-induced effects on telomerase and the sublethal damage repair capacity of the cells. 相似文献
9.
S E Sweigert K Eguchi-Kasai R L Warters L A Dethlefsen 《International journal of radiation biology》1989,56(3):253-264
We evaluated the relationship between the repair of DNA single- and double-strand breaks and cellular radiosensitivity in proliferating vs. quiescent cells of the mouse mammary tumor lines 66 and 67 in vitro, using the technique of filter elution at pH 12.2, pH 7.2 and pH 9.6. In these lines, quiescent (Q; unfed plateau-phase) cells are more radiosensitive than are proliferating (P) cells. At doses of 4-6 Gy, both 66 and 67 Q cells repair single-strand breaks (ssb) with kinetics similar to those of P cells. However, repair of ssb was slightly retarded in Q cells at a higher dose (10 Gy) than at the lower doses. In contrast, repair of ssb in P cells was dose-independent, at least for doses up to 10 Gy. The rate of repair of DNA double-strand breaks (dsb), measured at pH 7.2, was dose-independent in P and Q cells of both lines. The repair kinetics were biphasic, with an initial half-time less than 15 min, and the early phase was similar in all cell groups. The half-time for repair in the slow phase ranged from about 2 to greater than 20 h. The fraction of damage repaired by the slow phase was relatively high in all cell groups (40-70 per cent). In line 66, P cells repaired a higher percentage of dsb by 2 h postirradiation than did Q cells. The opposite was observed in line 67: Q cells repaired more dsb in 2 h than did P cells. The survival of 66 St4 cells (Q cultures which have been refed with complete medium and incubated 4 h) was significantly greater than that of 66 Q; nevertheless St4 cells repaired both ssb and dsb at rates similar to those of Q cells. Therefore, survival does not necessarily correlate with the rates of either ssb or dsb repair among these cell lines in different growth states. 相似文献
10.
A. M. GIUSTI 《International journal of radiation biology》2013,89(5):595-605
Purpose: To investigate the production and repair of lipid oxidative damage in two human cell lines exposed to acute and fractionated dose of ionizing radiation. Radiation dose was in the range from 0.1 to 44Gy. Materials and Methods: K562 and HL60 human cell lines have been used, 24 and 96 h after seeding. Membrane lipid oxidative damage has been detected by the measurement of the fluorescence decay of 1,6-diphenyl-1,3,5-hexatriene (DPH), its polarization value and the conjugated dienes concentration. The modification of DPH decay has been previously reported to be directly related to the lipid hydroperoxide concentration. Results: A modification of the DPH decay has been observed as a linear function of the logarithm of the radiation dose and only when the irradiation was performed in the presence of oxygen. The amount of the damage is related to the time after the cell medium change. By exposing the cells to fractionated radiation doses for several days (10 cGyday- 1), the oxidative damage has been found to be cumulative. After a single acute dose, evidence of repair of the lipid oxidative damage was not obtained. Conclusions: Following a previously developed method, the membrane damage was attributed to the production of hydroperoxide residues in the lipid acyl chains with the consequence of water penetration into the external portion of the bilayer, from the aqueous environment to the position of hydroperoxides. This damage is not repaired. The results obtained by measuring the DPH fluorescence decay have been compared with those obtained using other current optical and biochemical methods. None of these techniques could detect membrane oxidative damage at doses 10 Gy. Finally, the different sensitivity of 'young' and 'old' cells to the oxidative damage can be related to different cholesterol concentrations. 相似文献
11.
The in vitro cell survival of a human cervix carcinoma cell line (HX156c) has been assessed using 60Co gamma-rays administered at either high (150 cGy/min) or low (3.2 cGy/min) dose rate. Recovery during low dose-rate irradiation was observed; the dose reduction factor at 10(-2) cell kill for 150 versus 3.2 cGy/min was around 1.3. An insight into the possible underlying mechanisms of this recovery process has been investigated by addition of non-toxic concentrations of various agents thought to inhibit eukaryotic DNA repair. Agent were added 2 h prior to irradiation and removed after 24 h exposure. Differential effects among the inhibitors were observed; aphidicolin had no effect on cell survival, novobiocin, hydroxyurea and 3-aminobenzamide reduced survival by a similar extent at both dose rates, beta-ara A and caffeine reduced survival to a greater extent during low dose-rate irradiation. beta-ara A and caffeine seemed to exert their effects mainly by increasing the alpha component of the acute survival curve. Since survival curves obtained at dose rates of around 3 cGy/min help define a dominant component of the initial slope of the acute curve we have demonstrated that beta-ara A and caffeine modify the initial slope, probably by inhibiting DNA repair processes involved in the sparing of tumour cells during protracted irradiation. 相似文献
12.
SummaryJejunal crypt survival after fractionated total body irradiation of C3H mice given at dose rates between 1·2 and 0·08 Gy/min was studied and the results analysed according to the linear quadratic model. Whereas α was independent of dose rate β decreased with dose rate to approach zero at about 0·01 Gy/min.During the period of recovery, sublethal damage from doses given at high dose rate interact with low dose rate irradiation given immediately after, and increases its effectiveness. 相似文献
13.
Purpose
In order to clarify the biological response of tumor cells to proton beam irradiation, sublethal damage recovery (SLDR) and potentially lethal damage recovery (PLDR) induced after proton beam irradiation at the center of a 10?cm spread-out Bragg peak (SOBP) were compared with those seen after X?ray irradiation.Methods
Cell survival was determined by a colony assay using EMT6 and human salivary gland tumor (HSG) cells. First, two doses of 4?Gy/GyE (Gray equivalents, GyE) were given at an interfraction interval of 0–6?h. Second, five fractions of 1.6?Gy/GyE were administered at interfraction intervals of 0–5?min. Third, a delayed-plating assay involving cells in plateau-phase cultures was conducted. The cells were plated in plastic dishes immediately or 2–24?h after being irradiated with 8?Gy/GyE of X?rays or proton beams. Furthermore, we investigated the degree of protection from the effects of X?rays or proton beams afforded by the radical scavenger dimethyl sulfoxide to estimate the contribution of the indirect effect of radiation.Results
In both the first and second experiments, SLDR was more suppressed after proton beam irradiation than after X?ray irradiation. In the third experiment, there was no difference in PLDR between the proton beam and X?ray irradiation conditions. The degree of protection tended to be higher after X?ray irradiation than after proton beam irradiation.Conclusion
Compared with that seen after X?ray irradiation, SLDR might take place to a lesser extent after proton beam irradiation at the center of a 10?cm SOBP, while the extent of PLDR does not differ significantly between these two conditions.14.
PURPOSE: The difference in radiosensitivity between two isogenic tumour cell lines was evaluated to determine whether factors such as sublethal and potentially damage repair, DNA double-strand break repair and fidelity of repair can be related to differences in radiosensitivity. MATERIALS AND METHODS: The cell lines used were the ovarian carcinoma A2780s and a radiation-resistant derivative A2780cp. Radiation response was measured in terms of cell survival, recovery of sublethal (SLD) and potentially lethal damage (PLD), induction of and recovery of DNA strand breaks, and fidelity of DNA repair using a cell-free plasmid assay. RESULTS: While A2780cp was more resistant to radiation than A2780s, it showed less ability for recovery of SLD and PLD. DNA strand-break induction was the same for both cell lines, while only at very high doses did A2780cp show greater DNA strand-break recovery than A2780s. Fidelity of rejoining DNA was significantly higher in the A2780cp cell line. CONCLUSION: The difference in radiosensitivity between these two cell lines was not related to recovery of PLD or SLD or to the induction of DNA damage. It appears that fidelity of DNA rejoining, which was significantly higher in the resistant cell line, may be related to the difference in radiosensitivity. 相似文献
15.
D Bettega P Calzolari L Gariboldi P Pollara L Tallone Lombardi 《La Radiologia medica》1984,70(3):118-123
Survival, division delay and repair of sublethal damage were studied as a function of the cellular age in cells of EUE line exposed to 31 MeV protons, (LET of 1.83 keV/micron in tissue). The findings are compared with data reported in the literature on various mammalian cell lines exposed to X and gamma rays, common behaviours are pointed out and the characteristics parameters quantified. Survival varies with cell age and reaches a maximum value at mid S and its minimum at late G1; the ratio between maximum and minimum ranges between 1.5 and 15 depending on the survival level. Division delay resulted to be equal to 6 and 12% of the generation time per Gy for mid G1 and mid-late S respectively. All the investigated lines are able to repair as much as 50% of the sublethal damage within one hour. 相似文献
16.
Wang JZ Rhee JG Shi P Stewart RD Allen Li X 《International journal of radiation biology》2008,84(6):515-522
PURPOSE: The prolonged delivery times associated with intensity modulated radiation therapy (IMRT) may reduce treatment effectiveness of radiation therapy for cancers with short repair half-times. In this study, in vitro radiation experiments with DU-145 prostate cancer cells were designed to quantify the half-time of sublethal damage repair. METHOD AND MATERIALS: A series of single-fraction and split-dose clonogenic survival experiments were performed and analyzed using the linear-quadratic (LQ) survival model with mono-/two-component exponential and reciprocal-time repair kinetic models. RESULTS: Our data indicate that DU-145 cells are very radiosensitive (alpha = 0.44 Gy(-1), standard CI: 0.41-0.49 Gy(-1)) and are relatively insensitive to dose fractionation (alpha/beta = 16 Gy, standard CI: 12-34 Gy). The estimated repair half-time is 23 min (standard CI: 10-97 min) with some evidence that a small portion of the sublethal damage is repaired more slowly. CONCLUSION: The reported radiosensitivity parameters (alpha and alpha/beta) are larger than those derived from other in vitro experiments and clinical data. In contrast, the half-time for sublethal damage repair ( approximately 23 min) is close to the one derived from clinical data ( approximately 16 min). For such short repair half-times, the effectiveness of IMRT treatments may be substantially improved by decreasing the fraction delivery time. 相似文献
17.
Relationship between cellular radiosensitivity and DNA damage measured by comet assay in human normal, NBS and AT fibroblasts 总被引:2,自引:0,他引:2
PURPOSE: To study the relationship between cellular radiosensitivity and DNA damage measured by the comet assay. MATERIALS AND METHODS: Experiments were performed with nine human fibroblast lines (six normal, one NBS, and two AT). Cellular radiosensitivity was determined by colony assay and DNA damage was assessed by the comet assay. RESULTS: The cellular radiosensitivity of the fibroblast lines used covered a broad range with SF2 values varying between 1.3% and 53%. The comets analysed immediately after irradiation with doses up to 5 Gy showed marked differences among the cell lines; the relative initial tail moment at a dose of 5 Gy, ITM5, varied from 2.7+/-0.2 to 5.0+/-0.3. This variation was considered not to result from different numbers of DNA strand breaks induced but from differences in chromatin structure. There was an inverse correlation between SF2 and ITM5, i.e. radiosensitive cell lines exhibited a higher initial tail moment than radioresistant cell lines. In contrast, the repair kinetics measured with the comet assay for a dose of 2Gy followed by an incubation of up to 2h showed little variation and were found not to correlate with SF2. Repair kinetics as well as the amount of residual damage measured by this version of the comet assay were fairly similar to those measured by the alkaline unwinding technique and unlike that measured by neutral gel electrophoresis, indicating that this comet assay detects primarily single-strand breaks and alkali-labile sites, not double-strand breaks. CONCLUSIONS: The correlation between SF2 and the initial tail moment at 5 Gy found here suggests that the cellular radiosensitivity of human fibroblasts also depends on the chromatin structure. 相似文献
18.
E K Balcer-Kubiczek G H Harrison G H Zeman P J Mattson A Kunska 《International journal of radiation biology》1988,54(4):531-536
Exponential and density-inhibited cultures of C3H/10T1/2 cells were exposed to a single dose of 0.3 Gy of fission neutrons delivered at rates ranging from 0.005 to 0.1 Gy/min. No discernible effect upon cell survival or transformation was observed by a lowering of the fission neutron dose rate in either exponential or plateau cultures. At the level of 2.3 x 10(-4) transformants per surviving cell, the RBE for neoplastic transformation was three at acute dose rates and ten at the lowest dose rate studied (0.005 Gy/min for neutrons and 0.01 Gy/min for X-rays). 相似文献
19.
J.E. Coggle 《International journal of radiation biology》2013,89(2):229-232
SummaryThe in vitro cell survival of a human cervix carcinoma cell line (HX156c) has been assessed using 60Co γ-rays administered at either high (150 cGy/min) or low (3·2 cGy/min) dose rate. Recovery during low dose-rate irradiation was observed; the dose reduction factor at 10?2 cell kill for 150 versus 3·2 cGy/min was around 1·3. An insight into the possible underlying mechanisms of this recovery process has been investigated by addition of non-toxic concentrations of various agents thought to inhibit eukaryotic DNA repair. Agents were added 2 h prior to irradiation and removed after 24 h exposure. Differential effects among the inhibitors were observed; aphidicolin had no effect on cell survival, novobiocin, hydroxyurea and 3-aminobenzamide reduced survival by a similar extent at both dose rates, β-ara A and caffeine reduced survival to a greater extent during low dose-rate irradiation. β-ara A and caffeine seemed to exert their effects mainly by increasing the alpha component of the acute survival curve. Since survival curves obtained at dose rates of around 3 cGy/min help define a dominant component of the initial slope of the acute curve we have demonstrated that β-ara A and caffeine modify the initial slope, probably by inhibiting DNA repair processes involved in the sparing of tumour cells during protracted irradiation. 相似文献
20.