Mechanistic modelling of genetic and epigenetic events in radiation carcinogenesis

• Published in: Radiation protection dosimetry Vol. 122; no. 1-4; p. 335
• Main Authors: Andreev, S G, Eidelman, Y A, Salnikov, I V, Khvostunov, I K
• Format: Journal Article
• Language: English
• Published: England 01.12.2006
• Subjects: Alpha Particles; Animals; Cell Transformation, Neoplastic - pathology; Cell Transformation, Neoplastic - radiation effects; Computer Simulation; DNA - genetics; DNA - radiation effects; DNA Damage; Dose-Response Relationship, Radiation; Epigenesis, Genetic - genetics; Epigenesis, Genetic - radiation effects; Humans; Linear Energy Transfer - physiology; Linear Energy Transfer - radiation effects; Models, Genetic; Radiation Dosage; Radiometry - methods; Relative Biological Effectiveness
• ISSN: 0144-8420; 1742-3406
• DOI: 10.1093/rpd/ncl463

Methodological problems arise on the way of radiation carcinogenesis modelling with the incorporation of radiobiological and cancer biology mechanistic data. The results of biophysical modelling of different endpoints [DNA DSB induction, repair, chromosome aberrations (CA) and cell proliferation] are presented and applied to the analysis of RBE-LET relationships for radiation-induced neoplastic transformation (RINT) of C3H/10T1/2 cells in culture. Predicted values for some endpoints correlate well with the data. It is concluded that slowly repaired DSB clusters, as well as some kind of CA, may be initiating events for RINT. As an alternative interpretation, it is possible that DNA damage can induce RINT indirectly via epigenetic process. A hypothetical epigenetic pathway for RINT is discussed.