title: Modeling cell response to low doses of photon irradiation: Part 2--application to radiation-induced chromosomal aberrations in human carcinoma cells.
abstract: The biological phenomena observed at low doses of ionizing radiation (adaptive response, bystander effects, genomic instability, etc.) are still not well understood. While at high irradiation doses, cellular death may be directly linked to DNA damage, at low doses, other cellular structures may be involved in what are known as non-(DNA)-targeted effects. Mitochondria, in particular, may play a crucial role through their participation in a signaling network involving oxygen/nitrogen radical species. According to the size of the implicated organelles, the fluctuations in the energy deposited into these target structures may impact considerably the response of cells to low doses of ionizing irradiation. Based on a recent simulation of these fluctuations, a theoretical framework was established to have further insight into cell responses to low doses of photon irradiation, namely the triggering of radioresistance mechanisms by energy deposition into specific targets. Three versions of a model are considered depending on the target size and on the number of targets that need to be activated by energy deposition to trigger radioresistance mechanisms. These model versions are applied to the fraction of radiation-induced chromosomal aberrations measured at low doses in human carcinoma cells (CAL51). For this cell line, it was found in the present study that the mechanisms of radioresistance could not be triggered by the activation of a single small target (nanometric size, 100 nm), but could instead be triggered by the activation of a large target (micrometric, 10 μm) or by the activation of a great number of small targets. The mitochondria network, viewed either as a large target or as a set of small units, might be concerned by these low-dose effects.
authors.affiliation: Université de Lyon, 69622, Lyon, France.|Université de Lyon 1, Villeurbanne, France.|CNRS/IN2P3, Institut de Physique Nucléaire de Lyon, Villeurbanne, France.
authors.forename: Micaela
authors.identifier: http://orcid.org/0000-0003-4123-1502
authors.initials: M
authors.lastname: Cunha
authors.affiliation: Université de Lyon, 69622, Lyon, France.|Université de Lyon 1, Villeurbanne, France.|CNRS/IN2P3, Institut de Physique Nucléaire de Lyon, Villeurbanne, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Testa
authors.affiliation: Laboratory of Radiation Biology, Joint Institute for Nuclear Research, Dubna, Moscow Region, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Komova
authors.affiliation: Laboratory of Radiation Biology, Joint Institute for Nuclear Research, Dubna, Moscow Region, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Nasonova
authors.affiliation: Laboratory of Radiation Biology, Joint Institute for Nuclear Research, Dubna, Moscow Region, Russia.
authors.forename: Larisa A
authors.initials: LA
authors.lastname: Mel'nikova
authors.affiliation: Laboratory of Radiation Biology, Joint Institute for Nuclear Research, Dubna, Moscow Region, Russia.
authors.forename: Nina L
authors.initials: NL
authors.lastname: Shmakova
authors.affiliation: Université de Lyon, 69622, Lyon, France. m.beuve@ipnl.in2p3.fr.|Université de Lyon 1, Villeurbanne, France. m.beuve@ipnl.in2p3.fr.|CNRS/IN2P3, Institut de Physique Nucléaire de Lyon, Villeurbanne, France. m.beuve@ipnl.in2p3.fr.
authors.forename: Michaël
authors.initials: M
authors.lastname: Beuve
mesh_terms: D045744:Cell Line, Tumor; D002869:Chromosome Aberrations / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008954:Models, Biological; D017785:Photons
keywords: CAL51; Chromosomal aberrations; Low dose; Microdosimetry; Modeling; Nanodosimetry; Non-targeted effects; Radiation