title: Modeling of radiation action based on nanodosimetric event spectra.
abstract: Assuming that the number of ionizations events within short segments of DNA-size volumes is a major factor of the biological effectiveness of ionizing radiation, we have designed and manufactured a new nanodosimetric detector counting ionization events in small wall-less gas volumes, which simulate such DNA segments. The detector measures individual ionizations in low-pressure (~1 Torr) propane or any other gas corresponding to a tissue-equivalent cylindrical volume of 2-4 nm diameter and up to 30 nm length. While first nanodosimetric event spectra with protons and alpha particles are being obtained, it is important to develop and test a theory that relates these spectra to biological endpoints such as strand breakage, mutations, and lethal cellular events. This paper describes the two-compartment theory, which is based on the premise that energy deposition in nanometer sites can be broadly divided into two categories: a low-energy deposition compartment comprising events with a total number of 2-5 ionizations, and a high-energy deposition compartment comprising events containing 6-10 ionizations. Under standard biochemical conditions, these events will lead to different biological consequences. The fate of DNA lesions produced by low-energy deposition events will mostly depend on the repair capacity of the irradiated cells, whereas events produced by high-energy deposition events will be irreparable. These events are therefore the biologically most relevant lesions, since they inevitably lead to mutation and cell death.
authors.affiliation: Loma Linda University, Loma Linda, CA 92354, USA.
authors.forename: R
authors.initials: R
authors.lastname: Schulte
authors.forename: V
authors.initials: V
authors.lastname: Bashkirov
authors.forename: S
authors.initials: S
authors.lastname: Shchemelinin
authors.forename: G
authors.initials: G
authors.lastname: Garty
authors.forename: R
authors.initials: R
authors.lastname: Chechik
authors.forename: A
authors.initials: A
authors.lastname: Breskin
mesh_terms: D000818:Animals; D002478:Cells, Cultured / Q000528:radiation effects; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair; D016193:G1 Phase / Q000528:radiation effects; D006371:Helium; D018499:Linear Energy Transfer; D008954:Models, Biological; D011522:Protons; D011834:Radiation Monitoring / Q000295:instrumentation*; D012062:Relative Biological Effectiveness; D015203:Reproducibility of Results; D016196:S Phase / Q000528:radiation effects
chemical_list: D011522:Protons; D006371:Helium