title: [The enigma of the biological interpretation of the linear-quadratic model finally resolved? A summary for non-mathematicians].
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 β 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.
authors.affiliation: Inserm, UMR1052, centre de recherche en cancérologie de Lyon, bâtiment Cheney A, rue Laennec, 69008 Lyon, France.
authors.forename: L
authors.initials: L
authors.lastname: Bodgi
authors.affiliation: Inserm, UMR1052, centre de recherche en cancérologie de Lyon, bâtiment Cheney A, rue Laennec, 69008 Lyon, France; CNRS, UMR5208, institut Camille-Jordan, 69622 Villeurbanne, France.
authors.forename: A
authors.initials: A
authors.lastname: Canet
authors.affiliation: Inserm, UMR1052, centre de recherche en cancérologie de Lyon, bâtiment Cheney A, rue Laennec, 69008 Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Granzotto
authors.affiliation: Inserm, UMR1052, centre de recherche en cancérologie de Lyon, bâtiment Cheney A, rue Laennec, 69008 Lyon, France.
authors.forename: M
authors.initials: M
authors.lastname: Britel
authors.affiliation: Inserm, UMR1052, centre de recherche en cancérologie de Lyon, bâtiment Cheney A, rue Laennec, 69008 Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Puisieux
authors.affiliation: Institut de radioprotection et de sûreté nucléaire, 92262 Fontenay-aux-Roses, France.
authors.forename: M
authors.initials: M
authors.lastname: Bourguignon
authors.affiliation: Inserm, UMR1052, centre de recherche en cancérologie de Lyon, bâtiment Cheney A, rue Laennec, 69008 Lyon, France. Electronic address: nicolas.foray@inserm.fr.
authors.forename: N
authors.initials: N
authors.lastname: Foray
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects*; D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D016014:Linear Models; D008954:Models, Biological; D011836:Radiation Tolerance / Q000502:physiology* / Q000528:radiation effects
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins
keywords: ATM; DNA repair; LQ model; Modèle linéaire-quadratique; Radiosensibilité; Radiosensitivity; Réparation de l’ADN