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Nine human tumour cell lines (four mammary, one bladder, two prostate, one cervical, and one squamous cell carcinoma) were studied as to whether cellular radiosensitivity is related to the number of initial or residual double-strand breaks (dsb). Cellular sensitivity was measured by colony assay and dsb by means of constant- and graded-field gel electrophoresis (CFGE and GFGE, respectively). The nine tumour cell lines showed a broad variation in cellular sensitivity (SF2 0.17-0.63). The number of initial dsb as measured by GFGE ranged between 14 and 27 dsb/Gy/diploid DNA content. In contrast, normal fibroblasts raised from skin biopsies of seven individuals showed only a marginal variation with 18-20 dsb/Gy/diploid DNA content. For eight of the nine tumour cell lines, there was a significant correlation between the number of initial dsb and the cellular radiosensitivity. The tumour cells showed a broad variation in the amount of dsb measured 24 h after irradiation by CFGE, which, however, was not correlated with the cellular sensitivity. This residual damage was found to be influenced not only by the actual number of residual dsb, but also by apoptosis and cell cycle progression which had impact on CFGE measurements. Some cell line strains were able to proliferate even after exposure to 150 Gy while others were found to degrade their DNA. Our results suggest that for tumour cells, in contrast to normal cells, the variation in sensitivity is mainly determined by differences in the initial number of dsb induced. [ABSTRACT FROM AUTHOR]

Purpose: To provide an update on the recent knowledge about the molecular mechanisms of thermal radiosensitization and its possible relevance to thermoradiotherapy. Summary: Hyperthermia is probably the most potent cellular radiosensitizer known to date. Heat interacts with radiation and potentiates the cellular action of radiation by interfering with the cells' capability to deal with radiation-induced DNA damage. For ionizing irradiation, heat inhibits the repair of all types of DNA damage. Genetic and biochemical data suggest that the main pathways for DNA double-strand break (DSB) rejoining, non-homologous end-joining and homologous recombination, are not the likely primary targets for heat-induced radiosensitization. Rather, heat is suggested to affect primarily the religation step of base excision repair. Subsequently additional DSB arise during the DNA repair process in irradiated and heated cells and these additional DSB are all repaired with slow kinetics, the repair of which is highly error prone. Both mis- and non-rejoined DSB lead to an elevated number of lethal chromosome aberrations, finally causing additional cell killing. Heat-induced inhibition of DNA repair is considered not to result from altered signalling or enzyme inactivation but rather from alterations in higher-order chromatin structure. Although, the detailed mechanisms are not yet known, a substantial body of indirect and correlative data suggests that heat-induced protein aggregation at the level of attachment of looped DNA to the nuclear matrix impairs the accessibility of the damaged DNA for the repair machinery or impairs the processivity of the repair machinery itself. Conclusion: Since recent phase III clinical trials have shown significant benefit of adding hyperthermia to radiotherapy regimens for a number of malignancies, it will become more important again to determine the molecular effects underlying this success. Such information could eventually also improve treatment quality in terms of patient selection, improved sequencing of the heat and radiation treatments, the number of heat treatments, and multimodality treatments (i.e. thermochemoradiotherapy). [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the relation between double-strand breaks and thermal radiosensitization in dependence on cell-cycle position. Materials and methods: The experiments were performed with the human tumour cell line HeLa S3. Cells synchronized in G1- and S-phase were exposed to X-rays alone or in combination with prior heating at 44° C for 20 min. Cell kill was determined by means of colony forming assay, double-strand breaks (dsb) using constant-field gel electrophoresis and apoptotic cell death was scored using the fraction of detached cells. Results: In both cell-cycle phases heating at 44° C for 20min prior to irradiation resulted in an increased cellular radiosensitivity, whereby the thermal enhancement ratio (TER) was significantly higher in S- than in G1-phase cells with TER=2.1 and 1.2, respectively. Prior heating at 44° C did not affect the number of radiation-induced dsb but was found to modify their repair as measured for a X-ray dose of 40Gy. In both cell cycle phases dsb repair kinetics measured after irradiation alone could be described by a fast and a slow component with the majority of dsb being repaired with fast kinetics. Prior heating at 44° C was found to have only a minor effect on these half-times but mainly to affect the number of slowly rejoined dsb. In G1-phase cells the number of slowly rejoined dsb measured 300min after irradiation was enhanced by a factor of 1.8 and in S-phase cells even by a factor of 3.2. Fraction of apoptotically dying cells was low after X-irradiation alone but was clearly enhanced after combined treatment, which was especially pronounced for S-phase cells. Conclusions: The pronounced thermal radiosensitization found for S-phase cells was attributed to the heat-mediated increase in the number of slowly rejoined dsb and partly also to the enhanced fraction of apoptotically dying cells when compared to G1-phase cells. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to test under which conditions non-repaired DNA double-strand breaks (dsb) could be used as an indicator of cellular radiosensitivity of normal human fibroblasts. Materials and methods: The experiments were performed with a primary normal skin fibroblast line (NFHH) derived from a healthy donor. Cells were X-irradiated either in exponential or confluent state with high (4 Gy/min) or low dose rate (0.04Gy/min) and either plated immediately or delayed after irradiation. The fraction of clonogenic cells was determined after doses up to 12 Gy using colony forming assay and the number of non-repaired dsb were measured 24h after X-irradiation with doses up to 180 Gy using constant-field gel electrophoresis. Results: Cellular radiosensitivity of NFHH cells was found to depend on all three conditions tested. In contrast, the number of non-repaired dsb was found to depend on dose rate and growth state only. There were, however, no differences for the plating conditions tested. This result was attributed to the almost complete inhibition of cell-cycle progression when cells were plated immediately after irradiation. For the two dose rates and growth conditions, differences in non-repaired dsb were found to correspond with the respective differences measured for the cellular radiosensitivity, and these data agreed fairly well with the correlation previously found for 11 fibroblast lines varying in dsb repair capacity. Conclusions: For irradiation followed by delayed plating only, non-repaired dsb can be used to predict the cellular radiosensitivity. [ABSTRACT FROM AUTHOR]

Purpose: The radioprotective effect of the Bowman-Birk protease inhibitor (BBI) was previously shown to result from a TP53 dependent mechanism. Whether this effect involves specific DNA repair mechansims is now tested. Material and methods: Normal human fibroblasts were pre-treated with BBI before exposure to X-rays, UVB or to chemical agents (bleomycin, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), cisplatin). These agents were chosen because of their ability to induce different spectra of DNA damage. The radiometric agent bleomycin primarily induces double-strand breaks (dsb), which are repaired by recombination; MNNG results in alkylated bases which are repaired by base excision repair (BER); cisplatin results in DNA-crosslinks which are repaired mainly by nucleotide excision repair (NER); and finally UVB generates thymine dimers and thymine-cytosine-6-4 products which are also repaired by NER. Cell survival was analysed by colony formation assay and DNA dsb by constant field gel electrophoresis. The combined effect of BBI and X-rays was also tested for XP-fibroblasts, which are defective in NER. Results: For normal human fibroblasts the radioprotective effect of BBI was clearly found by using a delayed plating procedure. The radioprotective effect was found to be unrelated to an altered induction or repair of radiation-induced DNA dsb. Pre-treatment with BBI did not affect cell killing after exposure to bleomycin or MNNG, but resulted in a significant protection of cells exposed to cisplatin or UVB. These results indicate that pre-treatment with BBI did not alter recombination repair or BER, but was able to modify NER. The latter finding was supported by the observation made for XP-cells, where pre-treatment with BBI failed to result in radioprotection after exposure to ionizing radiation. Conclusions: On the basis of these data it is proposed that the radioprotective effect of BBI is the result of an improved nucleotide excision repair mechanism. [ABSTRACT FROM AUTHOR]

Purpose: To test the relationship between cell killing and nonrepaired DNA strand breaks both in repair proficient and deficient cell lines. Materials and methods: Five of the cell lines used are repair competent (CHO, CHO K1, rat rhabdomyosarcoma R1H, mouse balb and normal human fibroblasts), while four display a reduced repair capacity (scid, xrs 1, xrs 5, AT). Cell survival was determined by colony formation assay. The total number of strand breaks was measured by the alkaline unwinding technique and the numbers of double-strand breaks by constant-field gel electrophoresis. Results: The nine cell lines showed a broad spectrum in radiosensitivity with SF values ranging from 0.018 to 0.58. The cell lines 2 did not vary in the number of induced strand breaks, neither for all strand breaks nor for double-strand breaks alone. In contrast, there was a large variation in the number of non-repaired strand breaks measured 24 h after irradiation. Comparison of cell killing with the number of non-repaired breaks measured after a dose of 90 Gy showed no correlation for single-strand breaks ( r 2 0.29) but a fairly good correlation for double-strand breaks ( r 2 0.87). This correlation was found to hold both for repair proficient and deficient cell lines. Conclusions: The results obtained strongly suggest that the number of non-repaired double-strand breaks measured 24 h after irradiation can be used as an indicator of cellular radiosensitivity. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the correlation between PCC fragments and cell killing. Materials and methods: Induction and repair of DNA fragments were measured in CHO, CHO-K1, xrs 1 and xrs 5 cells using the premature chromosome condensation (PCC) technique and cell survival was determined by a colony assay. Results: The number of PCC fragments measured in cells immediately fused after X-irradiation was the same for CHO (3.4 0.16/cell/Gy) and CHO-K1 (3.6 0.12/cell/Gy) cells but significantly higher for xrs 1 (4.9 0.07/cell/Gy) and xrs 5 cells (7.0 0.4/cell/Gy). The repair curve of PCC fragments studied for CHO, CHO-K1 and xrs 5 cells was best described by a monophasic exponential decline with a final plateau; the halftime of this decline was always about 30 min. The number of unrejoined PCC fragments, which was measured 14 h after irradiation, increased linearly with dose. The steepest increase was found for xrs 5 cells (5.5 0.3 fragments per cell and per Gy), the lowest for CHO/CHO-K1 (0.9 0.1; 1.0 0.1) and for xrs 1 in between (3.3 0.1). For all four cell lines the relationship between cell killing and unrejoined fragments could be described by a single curve with a D0 of 2.5 0.4 unrejoined PCC fragments per lethal event. Conclusions: The data showed that the number of unrejoined PCC fragments can be used as an indicator of cellular radiosensitivity. [ABSTRACT FROM AUTHOR]

The DNA double-strand break (DSB) repair capacity of normal human fibroblasts was compared with that of cell lines with different genetic alterations. These cell lines are affected either in non-homologous end-joining (180BR), homology directed repair (C2352, C2395), base excision repair (CS1TAN, 46BR) or signalling (AT3, AT2BE, LFS2675, LFS2800, 95P558). Cellular radiosensitivity was determined by colony formation assay, DSB by constant-field gel electrophoresis and apoptosis was detected by caspase3 activity. For the mutated cell lines, the survival fraction at 2 Gy (SF2) varied between 0.013 and 0.49 in contrast to a variation of only 0.15 – 0.53 for normal fibroblasts. There was no variation in the number of initial DSB and only a small variation in the number of DSB remaining 24 h after irradiation. At 100 Gy, the latter number varied between 2 and 5 Gy-equivalents for normal fibroblasts and only between 3 and 7 Gy-equivalents for the mutated cell lines, corresponding to repair capacities of 95 – 98 and 93 – 97%, respectively. There were, however, two outliers (LFS2800, 180BR) where the number of remaining DSB was much higher with 22 and 30 Gy-equivalents, respectively. This elevated number resulted from a delayed repair and apoptotic cells. For all but these two cell lines, the relationship between the number of DSB remaining 24 h after irradiation and SF2 could be described by an identical correlation (r2 = 0.86, p < 0.0001). This result indicates that the relationship between DSB repair capacity and cellular radiosensitivity appears to be the same for normal and mutated cell lines, and that in both cases huge differences in cellular radiosensitivity result from only a very small variation in DSB repair capacity. [ABSTRACT FROM AUTHOR]

All biochemical and cytogenetic data on radiosensitization by heat treatment at and above 43°C indicate that inhibition of DNA repair plays a central role. There are several DNA repair pathways involved in restoration of damage after ionising irradiation and the kinetics of all of them are affected by heat shock. This, however, does not imply that the inhibition of each of these pathways is relevant to the effect of heat on cellular radiosensitivity. The current review evaluates the available data on heat radiosensitization in mutant or knockout cell lines defective in various DNA repair proteins and/or pathways. The data show that thermal inhibition of the non-homologous end-joining pathway (NHEJ) plays no role in heat radiosensitization. Furthermore, limited data suggest that the homologous recombination pathway may also not be a major heat target. By deduction, it is suggested that inhibition of base damage repair (BER) could be the crucial step in radiosensitization by heat. While a lack of mutant cell lines and redundancy of the BER pathway have hampered efforts toward a conclusive study, biochemical and correlative evidence support this hypothesis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract. The effect of heat (43-45 C) on the induction and the repair of DNA double-strand breaks (dsb) was studied in CHO cells after 60 Gy of X-rays using constant-field gel electrophoresis. Heat given prior to irradiation was found not to alter the number of dsb when measured immediately after irradiation. In non-heated cells, about 80% of all dsb were rapidly repaired with a half-time of 4 min, while 20% were repaired more slowly with T1/2=160 min. These kinetics were grossly altered by heat. Both the fast and the slow process were retarded. However, the main effect of heat was an increase in the number of slowly rejoined dsb. This increase was shown to result from the additional formation (up to 1.4-fold the initial number) of dsb early during the repair course. It is suggested that the additional dsb arose from base damage, the repair of which was unbalanced by heat. No evidence was found for apoptosis being involved in this process. The kinetics of the additional dsb was found to correlate with thermal radiosensitization. [ABSTRACT FROM AUTHOR]

Background To improve the outcome of patients with squamous cell carcinoma of the head and neck (HNSCC) and reduce the side effects of radiochemotherapy, the combination of target therapeutics with established chemoradiation protocols is under investigation. Sorafenib, a multikinase inhibitor, has a cytotoxic and antiproliferative effect as a monotherapy and acts as a radiosensitizer of HNSCC cell lines. As cisplatinbased chemoradiation is the standard treatment for locally advanced HNSCC, the aim of this study was to identify the influence of sorafenib on cisplatin + radiation treatment in HNSCC cell lines and to determine the effects on normal cells, to assess potential dose limiting toxicities. Material and methods Two different HNSCC cell lines (UT-SCC42A and UT-SCC42B) were treated by combination of Sorafenib (10 μ M; Nexavar®, Bayer) and Cisplatin (1–10 μ M) with/without irradiation (2–6 Gy). Cell number was assessed to determine the proliferation rate and colony formation assay was performed for estimation of cell survival. Fibroblasts (F180) were treated similarly to evaluate the cytotoxicity in non-tumor cells. Results Cisplatin has a dose-dependent antiproliferative effect in both cell lines. The growth inhibitory effect is clearly increased by addition of Sorafenib in a dose of 5 μ mol/l, according to a synergistic effect to cisplatin. In colony formation assay Cisplatin and Sorafenib have a dose-dependent cytotoxic effect in both cell lines. The combined treatment shows a sensitization of UT-SCC42A & 42B cells by Sorafenib against Cisplatin treatment, according to a chemosensitization. In both tested cell lines we observe a radiosensitization by sorafenib (10 μ mol/l) in presence of cisplatin (all tested doses), in contrast to only a minor radiosensitizing effect on HNSCC cells by Cisplatin alone. Fibroblasts (F180) were not affected by Sorafenib in terms of cell inactivation investigated in the colony formation assay. Conclusion Sorafenib acts as a radio- and chemosensitizer in two tested cell HNSCC cell lines and has no cytotoxic effect on normal fibroblasts. Therefore the combination of sorafenib with cisplatin-based chemoradiation may improve the efficacy of HNSCC treatment in terms of survival outcome and side effects. [ABSTRACT FROM AUTHOR]

Inhibition of homologous recombination (HR) is believed to be a transactivation-independent function of p53 that protects from genetic instability. Misrepair by HR can lead to genetic alterations such as translocations, duplications, insertions and loss of heterozygosity, which all bear the risk of driving oncogenic transformation. Regulation of HR by wild-type p53 (wtp53) should prevent these genomic rearrangements. Mutation of p53 is a frequent event during carcinogenesis. In particular, dominant-negative mutants inhibiting wtp53 expressed from the unperturbed allel can drive oncogenic transformation by disrupting the p53-dependent anticancer barrier. Here, we asked whether the hot spot mutants R175H and R273H relax HR control in p53-proficient cells. Utilizing an I-SceI-based reporter assay, we observed a moderate (1.5 × ) stimulation of HR upon expression of the mutant proteins in p53-proficient CV-1, but not in p53-deficient H1299 cells. Importantly, the stimulatory effect was exactly paralleled by an increase in the number of HR competent S- and G2-phase cells, which can well explain the enhanced recombination frequencies. Furthermore, the impact on HR exerted by the transactivation domain double-mutant L22Q/W23S and mutant R273P, both of which were reported to regulate HR independently of G1-arrest execution, is also exactly mirrored by cell-cycle behavior. These results are in contrast to previous concepts stating that the transactivation-independent impact of p53 on HR is a general phenomenon valid for replication-associated and also for directly induced double-strand break. Our data strongly suggest that the latter is largely mediated by cell-cycle regulation, a classical transactivation-dependent function of p53. [ABSTRACT FROM AUTHOR]

Presents a reply to a letter on the difference between tumor and normal cells in the induction and repair of DNA double-strand breaks. Variation of chromatin structure.

The aim was to study the relationship between cellular radiosensitivity or double-strand break (dsb) repair capacity of skin fibroblasts and the extent of acute reaction after radiotherapy for breast cancer. The study was performed with 25 breast cancer patients submitted to the radiotherapy unit of the Egyptian National Cancer Institute after conserving surgery. Dermal fibroblasts, established from skin biopsies, were used to determine the cellular radiosensitivity via colony assay and the capacity of dsb repair by constant-field gel electrophoresis. Acute reactions were scored using the Radiation Therapy Oncology Group (RTOG) classification. The spectrum of acute reactions varied from grade 1 to 4, whereby most patients developed a grade 1 reaction after total doses ranging between 46 and 70 Gy. Skin fibroblasts showed a pronounced variation in both cellular radiosensitivity expressed as the mean inactivation dose ( D bar ) (coefficient of variation, CV = 25%) as well as in the number of residual dsb (CV = 33%) with no significant correlation between these two endpoints ( r 2 = 0.20, p = 0.14). Both parameters did not correlate with the extent of acute reaction of the respective patient. The data obtained indicate that the sensitivity of fibroblasts measured either by colony assay or by dsb repair capacity is not a major parameter determining the extent of acute reaction after radiotherapy of breast cancer patients. [ABSTRACT FROM AUTHOR]

Purpose : To compare the induction and repair of radiation-induced base damage in human and rodent cell lines. Material and methods : Experiments were performed with two human (normal fibroblasts HSF1 and tumour HeLa cells) and two rodent (mouse L929 and hamster CHO-K1) cell lines. Base damage was determined with the alkaline comet assay combined with the repair enzyme formamidopyrimidine-glycosylase (Fpg). Proteins were detected by Western blot. Results : The induction of Fpg-sensitive sites was measured in human and rodent cell lines for doses up to 8 or 5 Gy, respectively. Comets were analysed in terms of tail moments, which were transformed into Gy-equivalents. The amount of Fpg-sensitive sites increased linearly with doses up to 4 Gy, whereby the ratio of single-strand breaks (ssb) to Fpg-sensitive sites was nearly identical for human and rodent cells with ssb:Fpg-sensitive sites=1:0.41±0.07 and 1:0.45±0.05, respectively. For doses exceeding 4 Gy, the amount of Fpg-sensitive sites did not increase further, indicating a dose limit up to which the comet assay can be used to detect Fpg-sensitive sites. Repair of Fpg-sensitive sites was studied for an X-ray dose of 4 Gy. For all four cell lines, the repair was measured to be completed 24 h after irradiation, but with pronounced differences in the kinetics. In both rodent cell lines, 50% of Fpg-sensitive sites were removed after t ½ =25±10 min in contrast to t ½ =80±20 min in the two human cell lines. The two species also differed in the level of polymerase ß with, on average, a three- to fivefold higher level in rodent cells compared with human cells. Conclusions : Repair of radiation-induced Fpg-sensitive sites was much faster in rodent than in human cells, which might result from the higher level of polymerase ß found in rodent cells. [ABSTRACT FROM AUTHOR]

The expression of theKu70 andKu80 genes as well as the activity of the DNA-dependent protein kinase (DNA-PK) were studied in 11 normal human fibroblast lines. The proteins studied are known to be part of a double-strand break (dsb) repair complex involved in non-homologous recombination, as was demonstrated for the radiosensitive rodent mutant cell lines of the complementation groups 5-7. The 11 fibroblast lines used in this study represent a typical spectrum of normal human radiosensitivity with the surviving fraction measured for a dose of 3.5 Gy, SF[SUB3.5 Gy], ranging from 0.03 to 0.28. These differences in cell survival were previously shown to correlate with the number of non-repaired dsbs. We found that the mRNA signal intensities of both Ku70 and Ku80 genes were fairly similar for the 11 cell lines investigated. In addition, the DNA-PK activity determined by the pulldown assay was fairly constant in these fibroblast lines. Despite the correlation between cell survival and dsb repair capacity, there was no correlation between dsb repair capacity and DNA-PK activity in the tested normal human fibroblast lines. Obviously, in this respect, other proteins/pathways appear to be more relevant. [ABSTRACT FROM AUTHOR]

Abstract. The effect of heat on double-strand breaks (dsb) repair was compared with thermal radiosensitization using HeLa S3 cells. Cells were exposed to a combined treatment of X-irradiation followed by heat (44 C, 0.5 h) separated by time intervals up to 8 h. DNA dsb were measured by PFGE and survival by the colony forming assay. In non-heated HeLa S3 cells repair of dsb was biphasic with the majority of breaks being repaired fast with a half-time of 14 min and only a minority were repaired slowly with a half-time of 130 min. Heat applied immediately after irradiation was found to cause an increase in both half-times but mainly to result in an increased fraction of slowly repairable dsb. The latter effect was shown to result from the formation of additional dsb. The number of additional dsb declined when irradiation and heat were separated by an interval at 37 C with a half-time of 120 30 min. This half-time was similar to the half-time of 100 20 min found for the loss of thermal radiosensitization studied for the same protocol. Both processes were recently found also to correlate in CHO cells but occurred much faster in rodent cells than in the human HeLa S3 cells used in the current study. These results show that in human cells, unlike previously suggested on the basis of rodent cells, thermal radiosensitization is still a substantial contributor to the killing efficacy of a combined treatment, even when irradiation and heat are separated by a time interval of 4 h. [ABSTRACT FROM AUTHOR]

Poster Highlights: Poster highlights 15: Particles and microbeams PH-0478: HPV pos HNSCC cells show strong radiosensitivity after photon but not after carbon ion irradiation S. Lerch, S. Berthold, F. Ziemann, K. Dreffke, F. Subtil, A. Jensen, R. Engenhart-Cabillic, E. Dikomey, A. Wittig, F. Eberle, U. Schötz. [Extracted from the article]

Poster Highlights: Poster highlights 7 RB: Novel radiobiological targets PH-0236: CD44v3-10 affects G2-arrest and radiosensitivity of S-phase cells via homologous recombination M. Al Bazaz, S. Lerch, R. Hannen, K. Lauber, E. Dikomey, R. Engenhart-Cabillic, U. Schötz. [Extracted from the article]