Numerical Simulations of Structural Chromosomal Instability
The origin of dose-response curves for radiation-induced chromosomal instability (CI) is studied using the mechanistic CI model. The model takes into account DNA damage generation and repair in the progeny of irradiated cells and cell passage through mitotic cycle. We consider the formation of DNA double-strand breaks (DSBs) de novo in the S phase, where predominantly chromatid-type aberrations are formed. Among them sister chromatid exchanges of the “isochromatid deletion” type, or “chromatid dicentrics” are of primary interest. When the cell enters mitosis, the fate of chromosomal aberrations depends on their types. Chromosomal and chromatid fragments, having entered mitosis, either are transmitted into one of the daughter cells, or are lost. A chromatid dicentric in mitosis forms an anaphase bridge. These mechanistic assumptions were used to demonstrate that the dose-response curves are closely related to the dynamic curves for CI. The principles underlying this relationship are analyzed.
UNSCEAR: Radiation-induced genomic instability. In: United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). Effects of Ionizing Radiation. UNSCEAR 2006 Report. Vol II, Annex C: Non-targeted and Delayed Effects of Exposure to Ionizing Radiation, pp. 5–22. United Nations, New York (2009), http://www.unscear.org/docs/publications/2006/UNSCEAR 2006 Annex-C.pdf
Kadhim, M., Salomaa, S., Wright, E., Hildebrandt, G., Belyakov, O.V., Prise, K.M., Little, M.P.: Non-targeted effects of ionising radiation – implications for low dose risk. Mutat. Res. 752(2), 84–98 (2013), DOI: 10.1016/j.mrrev.2012.12.001
Andreev, S.G., Eidelman, Y.A.: Dose-response prediction for radiation-induced chromosomal instability. Radiat. Prot. Dosim. 143(1–4), 270–273 (2011), DOI: 10.1093/rpd/ncq509
Andreev, S.G., Eidelman, Y.A., Salnikov, I.V., Slanina, S.V.: Modeling study of doseresponse relationships for radiation-induced chromosomal instability. Dokl. Biochem. Biophys. 451(1), 171–175 (2013), DOI: 10.1134/S1607672913040017