Correlation between cell reproductive death and chromosome aberrations assessed by FISH for low and high doses of radiation and sensitization by iodo-deoxyuridine in human SW-1573 cells

Franken, Nicolaas A.P.; Ruurs, P.; Ludwików, G.; Bree, Chris van; Kipp, J. B. A.; Darroudi, F.; Barendsen, G.W.

doi:10.1080/095530099140474

Cited by 32 publications

(25 citation statements)

References 32 publications

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“…The increase of the α-values for exponentially growing cells, as presented in our study, indicates an increase in the number of directly lethal events due to the HPs. This is in agreement with the observations of Webb et al (131) and Jones et al (94), which suggested that an important mechanism of radiosensitisation involves an increase of effective DNA DSBs (87,89,130). Miller et al (92,93) suggested that radiation-induced damage in cells which have HPs incorporated into the DNA after low-LET radiation resembles the damage produced by high-LET radiation.…”

Section: Discussionsupporting

confidence: 81%

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Cell survival and radiosensitisation: Modulation of the linear and quadratic parameters of the LQ model

Franken

Oei

Kok

et al. 2013

International Journal of Oncology

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Abstract.The linear-quadratic model (LQ model) provides a biologically plausible and experimentally established method to quantitatively describe the dose-response to irradiation in terms of clonogenic survival. In the basic LQ formula, the clonogenic surviving fraction S d ̸S 0 following a radiation dose d (Gy) is described by an inverse exponential approximation:, wherein α and β are experimentally derived parameters for the linear and quadratic terms, respectively. Radiation is often combined with other agents to achieve radiosensitisation. In this study, we reviewed radiation enhancement ratios of hyperthermia (HT), halogenated pyrimidines (HPs), various cytostatic drugs and poly(ADP-ribose) polymerase-1 (PARP1) inhibitors expressed in the parameters α and β derived from cell survival curves of various mammalian cell cultures. A significant change in the α/β ratio is of direct clinical interest for the selection of optimal fractionation schedules in radiation oncology, influencing the dose per fraction, dose fractionation and dose rate in combined treatments. The α/β ratio may increase by a mutually independent increase of α or decrease of β. The results demonstrated that the different agents increased the values of both α and β. However, depending on culture conditions, both parameters can also be separately influenced. Moreover, it appeared that radiosensitisation was more effective in radioresistant cell lines than in radiosensitive cell lines. Furthermore, radiosensitisation is also dependent on the cell cycle stage, such as the plateau or exponentially growing phase, as well as on post-treatment plating conditions. The LQ model provides a useful tool in the quantification of the effects of radiosensitising agents. These insights will help optimize fractionation schedules in multimodality treatments.

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Section: Discussionsupporting

confidence: 81%

“…Incorporation of halogenated pyrimidines (HPs), chloro-, bromo-and iodo-deoxyuridine (CldUrd, BrdUrd, IdUrd) into DNA is known to sensitise cells to ionizing radiation (6,8,11,(86)(87)(88)(89)(90)(91)(92)(93). The induced radiosensitisation increases with the degree of thymidine replacement.…”

Section: Halogenated Pyrimidinesmentioning

confidence: 99%

Cell survival and radiosensitisation: Modulation of the linear and quadratic parameters of the LQ model

Franken

Oei

Kok

et al. 2013

International Journal of Oncology

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“…These results on the decay of γ-H2AX foci as indicators of DNA DSBs and the correlation with PLDR are in agreement with this. In previous studies, we demonstrated a correlation between survival, chromosomal aberrations and PLDR, which was shown by a decrease in the value of α with higher survival and lower number of chromosomal aberrations [2,48]. In this study, we further demonstrated that there is an association between PLDRα and a decrease of DNA DSBs.…”

Section: Discussionsupporting

confidence: 61%

Decay of γ-H2AX foci correlates with potentially lethal damage repair and P53 status in human colorectal carcinoma cells

Oorschot

Oei

Nuijens

et al. 2014

Cellular and Molecular Biology Letters

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Abbreviations used: BrdUrd -bromodeoxyuridine; Cs -cesium; DAPI -4',6-diamidino-2-phenylindole; dp -delayed plating; DSB -double-strand breaks; FACS -fluorescent activated cell sorter; FCS -fetal bovine calfserum; HEPES -2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid; HPV -human papilloma virus; ip -immediate plating; PBSphosphate buffered saline; PLD -potentially lethal damage; PLDR -potentially lethal damage repair; PVDF -polyvinylidene fluoride; RIPA -radio immunoprecipitation assay; SDS PAGE -sodium dodecyl sulfate polyacrylamide gel electrophoresis; TNBS -PBS containing 0.1% Triton X-100 and 1% FCS Abstract:The influence of p53 status on potentially lethal damage repair (PLDR) and DNA double-strand break (DSB) repair was studied in two isogenic human colorectal carcinoma cell lines: RKO (p53 wild-type) and RC10.1 (p53 null). They were treated with different doses of ionizing radiation, and survival and the induction of DNA-DSB were studied. PLDR was determined by using clonogenic assays and then comparing the survival of cells plated immediately with the survival of cells plated 24 h after irradiation. Doses varied from 0 to 8 Gy. Survival curves were analyzed using the linear-quadratic formula: S(D)/S(0) = exp-(αD+βD 2 ). The γ-H2AX foci assay was used to study DNA DSB kinetics. Cells were irradiated with single doses of 0, 0.5, 1 and 2 Gy. Foci levels were studied in non-irradiated control cells and 30 min and 24 h after irradiation. Irradiation was performed with gamma rays from a 137 Cs source, with a dose rate of 0.5 Gy/min. The RKO cells show higher survival rates after delayed plating than after immediate plating, while no such difference was found for the RC10.1 cells. Functional p53 seems to be a relevant characteristic regarding PLDR for cell survival. Decay of γ-H2AX foci after exposure to ionizing radiation is associated with DSB repair. More residual foci are observed in RC10.1 than in RKO, indicating that decay of γ-H2AX foci correlates with p53 functionality and PLDR in RKO cells.

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“…Finally the cell suspension was dropped on precleaned slides and air-dried. PCC spreads were hybridized to whole chromosome-specific FITC labeled probes for chromosome 2 (Metasystems) using a previously described method (40,41). Slides were counterstained with DAPI (2.5 µg/ml) and embedded in antifade solution (Vectashield, Vector Laboratories, Burlingame, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Relative biological effectiveness of high linear energy transfer α-particles for the induction of DNA-double-strand breaks, chromosome aberrations and reproductive cell death in SW-1573 lung tumour cells

Franken

2011

Oncol Rep

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Abstract. Ionizing radiation-induced foci (IRIF) of DNA repair-related proteins accumulated at DNA double-strand break (DSB) sites have been suggested to be a powerful biodosimetric tool. However, the relationship between IRIF induction and biologically relevant endpoints, such as cell death and formation of chromosome rearrangements is less clear, especially for high linear energy transfer (LET) radiation. It is thus not sufficiently established whether IRIF are valid indicators of biological effectiveness of the various radiation types. This question is more significant in light of the recent advancements in light ion-beam and radionuclide therapy. Dose-effect relationships were determined for the induction of DNA-DSBs, chromosome aberrations and reproductive cell death in cultured SW-1573 cells irradiated with γ-rays from a Cs-137 source or with α-particles from an Am-241 source. Values of relative biological effectiveness (RBE) of the high LET α-particles were derived for these effects. DNA-DSB were detected by scoring of γ-H2AX foci, chromosome aberrations by fragments and translocations using premature chromosome condensation and cell survival by colony formation. Analysis of dose-effect relations was based on the linear-quadratic model. Except for the survival curves, for other effects no significant contribution was derived of the quadratic term in the range of doses up to 2 Gy of γ-rays. Calculated RBE values derived for the linear component of dose-effect relations for γ-H2AX foci, cell reproductive death, chromosome fragments and colour junctions are 1.0±0.3, 14.7±5.1, 15.3±5.9 and 13.3±6.0, respectively. RBE values calculated at a certain biological effect level are 1, 4, 13 and 13, respectively. The RBE values derived from the LQ model are preferred as they are based on clinically relevant doses. The results show that with low LET radiation only a small fraction of the numerous DNA-DSBs yield chromosome damage and reproductive cell death. It is concluded that many of the chromosomal aberrations detected by premature chromosome condensation do not cause reproductive cell death. Furthermore, RBE values for DNA-DSB detectable by γ-H2AX foci shortly after irradiation, provide no information relevant to applications of high LET radiation in radiotherapy. The RBE values of chromosome aberrations assessed by premature chromosome condensation are close to the value for reproductive cell death. This suggests possible relevance to assess RBE values for radiotherapy with high LET ions.

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Correlation between cell reproductive death and chromosome aberrations assessed by FISH for low and high doses of radiation and sensitization by iodo-deoxyuridine in human SW-1573 cells

Abstract: It can be concluded that the linear-quadratic analysis of dose-response relationships offers insights into the correlation between cell survival and induction of exchanges in non-sensitized and radiosensitized cells.

Cited by 32 publications

References 32 publications

Cell survival and radiosensitisation: Modulation of the linear and quadratic parameters of the LQ model

Cell survival and radiosensitisation: Modulation of the linear and quadratic parameters of the LQ model

Decay of γ-H2AX foci correlates with potentially lethal damage repair and P53 status in human colorectal carcinoma cells

Relative biological effectiveness of high linear energy transfer α-particles for the induction of DNA-double-strand breaks, chromosome aberrations and reproductive cell death in SW-1573 lung tumour cells

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