The Repair-Misrepair Model in Radiobiology: Comparison to Other Models

Tobias, Cornelius A.

doi:10.2307/3576635

Cited by 122 publications

(60 citation statements)

References 41 publications

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“…This result was demonstrated by several authors (17, 32–35) for the RMR (Repair-Misrepair) model (36), LPL (Lethal-Potentially Lethal) model (33), and more general binary misrepair models. In light of the conceptual similarities between the LQ model and other binary misrepair models, the fact that the corresponding formalisms make virtually equivalent predictions for dose-time relationships is not, in retrospect, particularly surprising.…”

Section: Is the Lq Model Correct?mentioning

confidence: 59%

The Linear-Quadratic Model Is an Appropriate Methodology for Determining Isoeffective Doses at Large Doses Per Fraction

Brenner

2008

Seminars in Radiation Oncology

468

336

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The tool most commonly used for quantitative predictions of dose / fractionation dependencies in radiotherapy is the mechanistically-based linear-quadratic (LQ) model. The LQ formalism is now almost universally used for calculating radiotherapeutic isoeffect doses for different fractionation/ protraction schemes. In summary, LQ has the following useful properties for predicting isoeffect doses: First, it is a mechanistic, biologically-based model; second, it has sufficiently few parameters to be practical; third, most other mechanistic models of cell killing predict the same fractionation dependencies as does LQ; fourth, it has well documented predictive properties for fractionation/doserate effects in the laboratory; fifth, it is reasonably well validated, experimentally and theoretically, up to about 10 Gy / fraction, and would be reasonable for use up to about 18 Gy per fraction. To date, there is no evidence of problems when LQ has been applied in the clinic.Let us start from the premise that we need some model for calculating iso-effect doses when alternate fractionation schemes are considered. In addition, apart from increasing interest in alternative fractionation/protraction schemes, it is essential that we know how to compensate appropriately for missed radiotherapy treatments.The tool most commonly used for quantitative predictions of dose / fractionation dependencies is the linear-quadratic (LQ) formalism (1-5). In radiotherapeutic applications, the LQ formalism is now almost universally used for calculating isoeffect doses for different fractionation/protraction schemes.In contrast to earlier methodologies, such as CRE, NSD and TDF (6,7), which were essentially empirical descriptions of past clinical data, the LQ formalism has become the preferred tool largely because it has a somewhat more biological basis, with tumor control and normal tissue complications specifically attributed to cell killing. By contrast, descriptive empirical models can go disastrously wrong if used outside the dose/fractionation range from which they were derived -as when NSD was applied to large doses per fraction (8,9).

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Section: Is the Lq Model Correct?mentioning

confidence: 59%

The Linear-Quadratic Model Is an Appropriate Methodology for Determining Isoeffective Doses at Large Doses Per Fraction

Brenner

2008

Seminars in Radiation Oncology

468

336

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“…Below we shall assume for simplicity that p(k) is just a constant independent of k, p(k) = η [36]. Note that being able to influence it is very important in both tumour and normal tissues.…”

Section: A Structured Population Modelling Approachmentioning

confidence: 99%

“…In 1989, Albright [1] converted the repair-misrepair (RMR) model [36] from a lumped model into a more accurate one which describes how individual cells evolve in time. The aim of the model was to calculate the probability that a cell will survive using a Markov process approach.…”

Section: The Albright Modelmentioning

confidence: 99%

“…that DSBs are produced if there are two SSBs located close together. In 1985, Tobias [36] formulated a kinetic model, the Repair-Misrepair (RMR) model, which takes into account DSB formation, repair and misrepair through linear and quadratic processes. In 1986, Curtis [7] formulated the lethal-potentially lethal (LPL) model which combines the approaches in TDRA and RMR formulations and was presented as a unified repair theory.…”

Section: Averaged (Non Individual-based) Cell Population Modelmentioning

confidence: 99%

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A mechanistic model of high dose irradiation damage

Siam

Grinfeld

Bahar

et al. 2018

Mathematics and Computers in Simulation

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“…Other Markov models of misrejoining DSBs [8,9] are stochastic extensions of a different classical kinetic model [10] corresponding to a Revell DSB misrejoining mechanism [11]. The SMBE model describes the dynamics of the probability that a nuclear site is in a specific state.…”

Section: The Smbe Modelmentioning

confidence: 99%

Time course solutions of the Sax-Markov binary eurejoining/misrejoining model of DNA double-strand breaks

Radivoyevitch¹

2000

Radiation and Environmental Biophysics

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The Sax-Markov binary eurejoining/misrejoining (SMBE) model is a stochastic representation of Sax's breakage-and-reunion mechanism of misrejoining DNA double-strand breaks (DSBs). In this model, to approximate DSB misrejoining probabilities that decrease with increasing distance, the nucleus is treated as a collection of eta isolated nuclear subvolumes called sites; DSB free ends within the same site interact with a probability that is independent of distance, and DSB free ends within different sites never interact. In our previous work, SMBE steady-state solutions were used to estimate eta from a combination of high-dose PFGE (pulsed-field gel electrophoresis) data and moderate-dose chromosomal aberration data. Here, analytic SMBE transient solutions (i.e., time courses of DSBs and misrejoinings) are derived and used to estimate eta from various sets of misrejoining DSB kinetic data. The time courses are multiexponentials with rate constants kappa, 6kappa, 15kappa, ... j(2j-1)kappa corresponding to different nuclear site states and not different types of DSBs. For example, the kappa component corresponds to nuclear sites with two DSB free ends and thus only one possible rejoining interaction, and the 6kappa component corresponds to sites with four DSB free ends and thus six (four choose two) potential rejoining interactions--four of these six potential interactions lead to a final state of two misrejoinings and the other two of six lead to a final state of correct repair (unrejoinable DSBs are not represented in the SMBE model). The SMBE time course solutions provide site number estimates that fall in the range of eta approximately equals 10-100 for premature chromosome condensation (PCC) data and eta approximately equals 1,000 for PFGE data.

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The Repair-Misrepair Model in Radiobiology: Comparison to Other Models

Cited by 122 publications

References 41 publications

The Linear-Quadratic Model Is an Appropriate Methodology for Determining Isoeffective Doses at Large Doses Per Fraction

The Linear-Quadratic Model Is an Appropriate Methodology for Determining Isoeffective Doses at Large Doses Per Fraction

A mechanistic model of high dose irradiation damage

Time course solutions of the Sax-Markov binary eurejoining/misrejoining model of DNA double-strand breaks

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