Physics to understand biology: Monte Carlo approaches to investigate space radiation doses and their effects on DNA and chromosomes

Exposure of biological structures to ionizing radiation can induce different damage types at various levels, from DNA and chromosomes up to cells, tissues, organs and entire organisms. Although these multi-step processes involve many orders of magnitude both in the space and in the time scale, the pattern of initial energy deposition in matter strongly influences the subsequent evolution of the process. Great help to elucidate the underlying mechanisms and to perform reliable predictions is provided by mechanistic models and Monte Carlo codes, which allow one to take into account the stochastic aspects characterizing energy deposition in matter. Concerning radiation damage at the level of tissues and organs, in this paper we will focus on organ doses to astronauts exposed to Galactic Cosmic Rays (GCR) in deep space, under different shielding conditions. The calculations were carried out by means of the FLUKA transport and interaction MC code, coupled with two anthropomorphic model phantoms inserted into an Al shielding box of variable thickness. Besides organ-averaged absorbed doses and dose equivalents we calculated “biological doses”, defined as yields of clustered DNA breaks (“Complex Lesions”) in a given organ. CL have been obtained by “event-by-event” radiation track-structure simulations at the nm level and they are integrated on-line into a purposely modified version of FLUKA, which adopts a “condensed-history” approach. To quantify the role of nuclear interactions, for each shield thickness the dose contributions from secondary hadrons (including ions) were calculated separately. Furthermore, the neutron contribution was separated from that of all other nuclear reaction products. Concerning damage at the molecular and cellular level, herein we will present and discuss examples of application of a Monte Carlo code developed at the University of Pavia, which can simulate chromosome aberration induction by different radiation types. The focus will be both on the role played by the particle track structure at the nm level and on the relationship between aberrations and relevant cellular endpoints such as cell death and cell conversion to malignancy. Main assumption of the model is the hypothesis that only clustered lesions (CLs) of the DNA double-helix can “evolve” and lead to aberrations. A combination of the two approaches (condensed-history and event-by-event) allowed estimation of yields of chromosome aberrations following exposure to GCR in deep space, which were found to be consistent with aberration yields observed in lymphocytes of astronauts involved in long-term missions onboard the Mir station and the International Space Station.