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1.
Cancer Radiother ; 20(4): 314-21, 2016 Jun.
Article in French | MEDLINE | ID: mdl-27342947

ABSTRACT

The linear-quadratic (LQ) model is the only mathematical formula linking cellular survival and radiation dose that is sufficiently consensual to help radiation oncologists and radiobiologists in describing the radiation-induced events. However, this formula proposed in the 1970s and α and ß parameters on which it is based remained without relevant biological meaning. From a collection of cutaneous fibroblasts with different radiosensitivity, built over 12 years by more than 50 French radiation oncologists, we recently pointed out that the ATM protein, major actor of the radiation response, diffuses from the cytoplasm to the nucleus after irradiation. The evidence of this nuclear shuttling of ATM allowed us to provide a biological interpretation of the LQ model in its mathematical features, validated by a hundred of radiosensitive cases. A mechanistic explanation of the radiosensitivity of syndromes caused by the mutation of cytoplasmic proteins and of the hypersensitivity to low-dose phenomenon has been proposed, as well. In this review, we present our resolution of the LQ model in the most didactic way.


Subject(s)
Ataxia Telangiectasia Mutated Proteins/metabolism , Cell Survival/radiation effects , Linear Models , Radiation Tolerance/physiology , Cell Survival/physiology , DNA Damage/physiology , DNA Repair/physiology , DNA Repair/radiation effects , Dose-Response Relationship, Radiation , Humans , Models, Biological , Radiation Tolerance/radiation effects
2.
Cancer Radiother ; 20(3): 217-25, 2016 May.
Article in French | MEDLINE | ID: mdl-27020715

ABSTRACT

The dose fractionation effect is a recurrent question of radiation biology research that remains unsolved since no model predicts the clinical effect only with the cumulated dose and the radiobiology of irradiated tissues. Such an important question is differentially answered in radioprotection, radiotherapy, radiology or epidemiology. A better understanding of the molecular response to radiation makes possible today a novel approach to identify the parameters that condition the fractionation effect. Particularly, the time between doses appears to be a key factor since it will permit, or not, the repair of certain radiation-induced DNA damages whose repair rates are of the order of seconds, minutes or hours: the fractionation effect will therefore vary according to the functionality of the different repair pathways, whatever for tumor or normal tissues.


Subject(s)
DNA Repair/radiation effects , Dose Fractionation, Radiation , Radiation Dosage , Time Factors
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