181 Physica Medica - Vol. XVII, Supplement 1, 2001 A model of radiation-induced myelopoiesis in space R.D. Esposito 1 , M. Durante 1 , G. Gialanella 1 , G. Grossi 1 , M. Pugliese 1 , P. Scampoli 1 , T.D. Jones 2 1. Department of Physics, University “Federico II”, Dipartimento di Scienze Fisiche, Complesso universitario di Monte S. Angelo, Via Cintia, 80126 Napoli (Italy) 2. Oak Ridge National Laboratory, TN (USA) Abstract Astronauts’ radiation exposure limits are based on experimental and epidemiological data obtained on Earth. It is assumed that radiation sensitivity remains the same in the extraterrestrial space. However, human radiosensitivity is dependent upon the response of the hematopoietic tissue to the radiation insult. It is well known that the immune system is affected by microgravity. We have developed a mathematical model of radiation-induced myelopoiesis which includes the effect of microgravity on bone marrow kinetics. It is assumed that cellular radiosensitivity is not modified by the space environment, but repopulation rates of stem and stromal cells are reduced as a function of time in weightlessness. A realistic model of the space radiation environment, including the HZE component, is used to simulate the radiation damage. A dedicated computer code was written and applied to solar particle events and to the mission to Mars. The results suggest that altered myelopoiesis and lymphopoiesis in microgravity might increase human radiosensitivity in space. KEYWORDS: Myelopoiesis, space radiation, microgravity, computer code. 1. Introduction Radiation risk to crews of long-term manned space missions are estimated using biophysical models of radiation action. In these models, the space radiation environment is carefully simulated, but the indivi- dual radiosensitivity is assumed to be the same on earth and in space. The hematopoietic tissue is the main radiation target for both acute radiation effects (e.g. in case of a solar particle event) and late stochastic risk (caused by low-dose chronic expo- sure to space radiation). It is known that the immune system function is altered in microgravity [1], yet so far this effect has not been considered in the estimates of astronauts’ radiosensitivity. We have modified a mathematical model of ra- diation-induced myelopoiesis, which has been widely used to describe the radiosensitivity of humans and animals on Earth [2]. The new model, tested on cancer patients’ data treated with radiotherapy, describes the effect of whole and partial-body expo- sure, both on myelopoiesis and lymphopoiesis. Moreover it allows to consider the microgravity effects of bone marrow kinetics. An equivalent whole body prompt dose (EPD) for any reference radiation, i.e. the dose that would cause the same hematopoietic injury of a prompt exposure, is cal- culated for each exposure scenario. 2. The model Hematopietic cells are compartmentalised into nor- mal (n), injured (i), and killed (k). Process by which these populations change are modelled by a set of three differential equations. The five l xy parameters in these equations describe the transition rates among compartments (from x to y compartment) and are cell- and radiation-type dependant. Parameters can be evaluated for each exposure scenario. We assume that cellular radiosensitivity is not modified by space environment, but repopulation rates (l nn ) of stem and stromal cells are reduced as a function of time in weightlessness. We assume that l nn varies with time as l nn (t) = l nn (0) e –t/t where l nn (0) is the value in normal conditions and l is calculated from the experimental value of l nn after a certain time in weightlessness. We used an 84% decrease after two weeks in space from pu- blished data [3]. The complex space radiation filed has been divided into two main components: a low-LET component (parameters are calculated from 60 Co g- rays) and a high-LET component (parameters are calculated from fission neutrons) [4]. The values of the five parameters, for a given cellular type, are obtained as a weighted mean of the values of the parameters for the single components (Table I) using the dose rates of each component (Table II) as weights. GCR (cGy/min) SPE (cGy/min) Shielding Low-LET High-LET Low-LET High-LET 5 g/cm 2 Al 1.54·10 -5 8.50·10 -6 3.92·10 -2 4.30·10 -3 Mars Surface 8.33·10 -6 2.43·10 -6 5.90·10 -3 5.21·10 -4 Table I – Dose rates for each component of GCR and SPE radiation. These data refer to the period of minimum solar activity during which SPE should be rarer. The 5 g/cm 2 Aluminium shielding is the most likely to be used. 1 st International Workshop on Space Radiation Research and 11 th Annual NASA Space Radiation Health Investigators’ Workshop Arona (Italy), May 27-31, 2000