Modeling cell response to low doses of photon irradiation: Part 2—application to radiation-induced chromosomal aberrations in human carcinoma cells

• Published in: Radiation and environmental biophysics Vol. 55; no. 1; pp. 31 - 40
• Main Authors: Cunha, Micaela, Testa, Etienne, Komova, Olga V., Nasonova, Elena A., Mel’nikova, Larisa A., Shmakova, Nina L., Beuve, Michaël
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2016; Springer Nature B.V
• Subjects: Biological and Medical Physics; Biophysics; Cancer; Cell Line, Tumor; Cellular biology; Chromosome Aberrations - radiation effects; Chromosomes; Dose-Response Relationship, Radiation; Dosimetry; Ecosystems; Effects of Radiation/Radiation Protection; Environmental Physics; Humans; Models, Biological; Monitoring/Environmental Analysis; Original Article; Photons; Physics; Physics and Astronomy; Radiation therapy; Nanodosimetry; Microdosimetry; CAL51; Chromosomal aberrations; Low dose; Non-targeted effects; Radiation; Modeling
• ISSN: 0301-634X; 1432-2099
• DOI: 10.1007/s00411-015-0622-5

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 μ m ) 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.