Involvement of the Artemis protein in the relative biological efficiency observed with the 76-MeV proton beam used at the Institut Curie Proton Therapy Center in Orsay.
International Journal of Radiation Oncology*Biology*Physics. 2014-09-01; 90(1): 36-43
DOI: 10.1016/j.ijrobp.2014.05.018
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1. Int J Radiat Oncol Biol Phys. 2014 Sep 1;90(1):36-43. doi:
10.1016/j.ijrobp.2014.05.018.
Involvement of the Artemis protein in the relative biological efficiency observed
with the 76-MeV proton beam used at the Institut Curie Proton Therapy Center in
Orsay.
Calugaru V(1), Nauraye C(2), Cordelières FP(3), Biard D(4), De Marzi L(2), Hall
J(5), Favaudon V(5), Mégnin-Chanet F(6).
Author information:
(1)Institut Curie Centre de Protonthérapie d’Orsay, Centre Universitaire, Orsay,
France; Institut Curie, Centre Universitaire, Orsay, France; INSERM U612, Centre
Universitaire, Orsay, France.
(2)Institut Curie Centre de Protonthérapie d’Orsay, Centre Universitaire, Orsay,
France.
(3)Institut Curie, Centre Universitaire, Orsay, France.
(4)Centre d’Etude Atomique, Direction des Sciences du Vivant, Institut des
Maladies Emergentes et des Thérapies Innovantes, Service d’Etude des Prions et
des Infections Atypiques, Fontenay-aux-Roses, France.
(5)Institut Curie, Centre Universitaire, Orsay, France; INSERM U612, Centre
Universitaire, Orsay, France.
(6)Institut Curie, Centre Universitaire, Orsay, France; INSERM U612, Centre
Universitaire, Orsay, France. Electronic address: .
Erratum in
Int J Radiat Oncol Biol Phys. 2015 Feb 1;91(2):457.
PURPOSE: Previously we showed that the relative biological efficiency for induced
cell killing by the 76-MeV beam used at the Institut Curie Proton Therapy Center
in Orsay increased with depth throughout the spread-out Bragg peak (SOBP). To
investigate the repair pathways underlying this increase, we used an isogenic
human cell model in which individual DNA repair proteins have been depleted, and
techniques dedicated to precise measurements of radiation-induced DNA
single-strand breaks (SSBs) and double-strand breaks (DSBs).
METHODS AND MATERIALS: The 3-Gy surviving fractions of HeLa cells individually
depleted of Ogg1, XRCC1, and PARP1 (the base excision repair/SSB repair pathway)
or of ATM, DNA-PKcs, XRCC4, and Artemis (nonhomologous end-joining pathway) were
determined at the 3 positions previously defined in the SOBP. Quantification of
incident SSBs and DSBs by the alkaline elution technique and 3-dimensional (3D)
immunofluorescence of γ-H2AX foci, respectively, was performed in SQ20 B cells.
RESULTS: We showed that the amount of SSBs and DSBs depends directly on the
particle fluence and that the increase in relative biological efficiency observed
in the distal part of the SOBP is due to a subset of lesions generated under
these conditions, leading to cell death via a pathway in which the Artemis
protein plays a central role.
CONCLUSIONS: Because therapies like proton or carbon beams are now being used to
treat cancer, it is even more important to dissect the mechanisms implicated in
the repair of the lesions generated by these particles. Additionally, alteration
of the expression or activity of the Artemis protein could be a novel therapeutic
tool before high linear energy transfer irradiation treatment.
Copyright © 2014 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.ijrobp.2014.05.018
PMID: 25195988 [Indexed for MEDLINE]