title: A single formula to describe radiation-induced protein relocalization: towards a mathematical definition of individual radiosensitivity.
abstract: Immunofluorescence with antibodies against DNA damage repair and signaling protein is revolutionarising the estimation of the genotoxic risk. Indeed, a number of stress response proteins relocalize in nucleus as identifiable foci whose number, pattern and appearance/disappearance rate depend on several parameters such as the stress nature, dose, time and individual factor. Few authors proposed biomathematical tools to describe them in a unified formula that would be relevant for all the relocalizable proteins. Based on our two previous reports in this Journal (Foray et al., 2005; Gastaldo et al., 2008), we considered that foci response to stress is composed of a recognition and a repair phase, both described by an inverse power function provided from a Euler's Gamma distribution. The resulting unified formula called "Bodgi's function" is able to describe appearance/disappearance kinetics of nuclear foci after any condition of genotoxic stress. By applying the Bodgi's formula to DNA damage repair data from 45 patients treated with radiotherapy, we deduced a classification of human radiosensitivity based on objective molecular criteria, notably like the number of unrepaired DNA double-strand breaks and the radiation-induced nucleo-shuttling of the ATM kinase.
authors.affiliation: Institut national de la Santé et de la Recherche Médicale, UMR1052-Radiobiology Group, Cancer Research Centre of Lyon, 28 Rue Laennec 69008, Lyon, France.
authors.forename: Larry
authors.initials: L
authors.lastname: Bodgi
authors.forename: Adeline
authors.initials: A
authors.lastname: Granzotto
authors.forename: Clément
authors.initials: C
authors.lastname: Devic
authors.forename: Guillaume
authors.initials: G
authors.lastname: Vogin
authors.forename: Annick
authors.initials: A
authors.lastname: Lesne
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bottollier-Depois
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Victor
authors.forename: Mira
authors.initials: M
authors.lastname: Maalouf
authors.forename: Georges
authors.initials: G
authors.lastname: Fares
authors.forename: Nicolas
authors.initials: N
authors.lastname: Foray
mesh_terms: D000974:Antibodies, Antinuclear / Q000737:chemistry; D004249:DNA Damage; D004260:DNA Repair; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005720:Gamma Rays / Q000009:adverse effects*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D021381:Protein Transport / Q000528:radiation effects; D011836:Radiation Tolerance / Q000528:radiation effects*; D011878:Radiotherapy / Q000009:adverse effects; D014965:X-Rays / Q000009:adverse effects
chemical_list: D000974:Antibodies, Antinuclear
keywords: DNA repair; Immunofluorescence; Radiation; Radiosensitivity