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

Franken, Nicolaas A.P.; Oei, Arlene L.; Kok, H. Petra; Rodermond, Hans M.; Sminia, Peter; Crezee, J.; Stalpers, Lukas J.A.; Barendsen, G.W.

doi:10.3892/ijo.2013.1857

Cited by 94 publications

(93 citation statements)

References 117 publications

(160 reference statements)

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“…RKO cells with wildtype p53 protein clearly demonstrated PLDR while the RC10.1 cell line with a p53 null status showed reduced PLDR. These findings correspond to data presented earlier [19,25]. The obtained PLDR-α values were 1.4  0.2 and 1.0  0.2 for RKO and RC10.1 cells, respectively, which are almost identical to the values observed in a previous study 1.7  0.3 and 1.1  0.2 [19].…”

Section: Discussionsupporting

confidence: 81%

“…The difference in survival rates of ip and dp cells is considered to represent the cells' capacity for repairing potentially lethal DNA damage. Quantitative information about cultured cells can be analyzed in terms of mathematical dose-effect relationships based on the linear-quadratic (LQ) model of cell reproductive death as a function of the radiation dose [25][26][27][28]. The LQ-formula for the cell reproductive death of cells is described by an inverse exponential approximation:…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

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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“…In vitro experiments for radiation combined with either halogenated pyrimidines and hyperthermia or with cisplatin and hyperthermia have been published in several earlier communications Franken et al 2001Franken et al , 2013. In this study we performed linear quadratic analyses on these published data and evaluated enhancement factors of the LQparameters, which reflect the increase in radiation sensitivity as a result of the combined treatment.…”

Section: Methodsmentioning

confidence: 99%

Analysis of enhancement at small and large radiation doses for effectiveness of inactivation in cultured cells by combining two agents with radiation

Franken

Kok

Crezee

et al. 2016

International Journal of Radiation Biology

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Purpose: To evaluate the enhancement effect of two combined radiation-sensitizing agents in mammalian cells at small doses as compared to large doses using the linear-quadratic (LQ) mathematical model. Methods and materials: Data on clonogenic assays concerning the radio-enhancement effects of combined halogenated pyrimidines and hyperthermia or combined cisplatin and hyperthermia, as published in earlier reports, were analyzed according to the LQ-formula:). Effects of sensitizing agents on the linear parameter a and the quadratic parameter b are compared in order to evaluate differences depending on the applied dose, the possible relations to mechanisms of radiation sensitization and to derive suggestions for applications. Results: The values of the linear parameter a, which determines the effectiveness at low doses, are for all cell lines and all conditions more increased than the values of the parameter b which has a higher contribution at larger radiation doses. The combination of hyperthermia with halogenated pyrimidines to radiation as well as the combination of hyperthermia and cisplatin to radiation significantly increases the value of the linear parameter a, as compared to radiation alone or radiation combined with a single agent. Conclusions:The radiation enhancement factors of the values of linear and quadratic parameters demonstrate that the sensitizing agents have a larger effect on the linear parameter which is dominant at low radiation doses as is used in fractionated-radiation treatment in the clinic. Moreover, the effect is even further increased when two radiation sensitizers are used. ARTICLE HISTORY

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“…Whereas TER values have been frequently reported, LQ parameters under HT conditions are less readily available and if they are available often just for a single temperature level [50], and Myerson et al used this result in a prospective study to analyse the thermal dose escalation for 60 patients treated with simultaneous hyperthermia and radiotherapy [51]. A review of available LQ data under HT conditions is given by Franken et al [52,53]. These data represent the mechanisms of inhibition of DNA damage repair and of direct cell killing.…”

Section: Modelling Of Ht Mechanisms Using the Lq Modelmentioning

confidence: 99%

Thermoradiotherapy planning: Integration in routine clinical practice

Crezee

Leeuwen

Oei

et al. 2015

International Journal of Hyperthermia

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Planning of combined radiotherapy and hyperthermia treatments should be performed taking the synergistic action between the two modalities into account. This work evaluates the available experimental data on cytotoxicity of combined radiotherapy and hyperthermia treatment and the requirements for integration of hyperthermia and radiotherapy treatment planning into a single planning platform. The underlying synergistic mechanisms of hyperthermia include inhibiting DNA repair, selective killing of radioresistant hypoxic tumour tissue and increased radiosensitivity by enhanced tissue perfusion. Each of these mechanisms displays different dose-effect relations, different optimal time intervals and different optimal sequences between radiotherapy and hyperthermia. Radiosensitisation can be modelled using the linear-quadratic (LQ) model to account for DNA repair inhibition by hyperthermia. In a recent study, an LQ model-based thermoradiotherapy planning (TRTP) system was used to demonstrate that dose escalation by hyperthermia is equivalent to $10 Gy for prostate cancer patients treated with radiotherapy. The first step for more reliable TRTP is further expansion of the data set of LQ parameters for normally oxygenated normal and tumour tissue valid over the temperature range used clinically and for the relevant time intervals between radiotherapy and hyperthermia. The next step is to model the effect of hyperthermia in hypoxic tumour cells including the physiological response to hyperthermia and the resulting reoxygenation. Thermoradiotherapy planning is feasible and a necessity for an optimal clinical application of hyperthermia combined with radiotherapy in individual patients.

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

Cited by 94 publications

References 117 publications

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

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

Analysis of enhancement at small and large radiation doses for effectiveness of inactivation in cultured cells by combining two agents with radiation

Thermoradiotherapy planning: Integration in routine clinical practice

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