RBE and genetic susceptibility of mouse and rat spermatogonial stem cells to protons, heavy charged particles and 1.5 MeV neutrons

Abstract

The main purpose of the present study is to provide data on RBE and genetic susceptibility in the mouse and the rat when exposed to protons, HZE particles and neutrons.

Genetic damage from exposure to 50 MeV and 9 GeV protons, 4 GeV/nucleon helium ions, 4 GeV/nucleon carbon ions and 1.5 MeV neutrons was studied in adult (CBA × C57Bl/6J) F1 mice. Damage from 9 GeV protons and 4 GeV helium ions was studied in adult Wistar rats. The incidence of reciprocal translocations (RT) induced in the spermatogonial stem cells of each species was recorded. RBE values were derived by comparing linear regression coefficients from dose–responses within the same dose-range for each of the radiation types tested and ⁶⁰Co γ-rays or by means of a direct nonparametric method.

RT yields measured after mouse and rat spermatogonial irradiation with protons, heavy charged particles and neutrons fit the linear model of the dose–response relationship. Relative to ⁶⁰Co γ-rays, RBE values are as follows for mouse spermatogonia: 0.9 for 50 MeV protons; 1.3 for 9 GeV protons; 0.7 for 4 GeV helium ions; and 1.3 for 4 GeV carbon ions. For rat spermatogonia, values were: 1.7 for 9 GeV protons and 1.3 for helium ions. Compared to mice irradiated using the same experimental design, rats were more susceptible to high-LET radiations, with susceptibility assessed by genetic damage to their spermatogonial stem cells. The RBE of 1.5 MeV neutron is about 6.6.

Introduction

Reciprocal translocations (RT) in mammalian spermatogonia are a well-established, classical endpoint in radiobiology, and assessing RT in mammalian spermatogonia is considered to be a reliable approach for predicting genetic radiation risk through the so called “direct method”. Reciprocal translocation is the only endpoint for which limited data have been obtained after induction in irradiated human spermatogonia. Experiments designed mainly to evaluate the genetic effectiveness (RBE) of different levels of low- and high-LET radiation were started at the beginning of 1972 as a common scientific program between the Institute of Biomedical Problems (IBP) at the Joint Institute for Nuclear Research (JINR) in Dubna, Russia, and the National Centre of Radiobiology and Radiation Protection (NCRRP) in Bulgaria. Since then, the radiation genetics laboratory at Bulgaria’s NCRRP has analyzed the effects of exposure to different kinds of irradiation, including irradiation during real space flights, on various mammalian species. A portion of the results of these experiments has been published in a final (Benova, 1987, Bajrakova et al., 1974, Bajrakova et al., 1976a, Bajrakova et al., 1976b) or preliminary design (Baev et al., 1973). Another portion, mainly relating to the effects of irradiation during space flights or low- and high-LET radiation exposure in accelerators, remains unpublished or partially reported in Russia (Bajrakova and Fedorenko, 1991, Benova et al., 1985) and in Bulgaria (Nikolov et al., 1985, Pantev et al., 1980, Vaglenov, 1985, Vaglenov and Serova, 1987, Vaglenov et al., 1986, Vaglenov et al., 1989).

This information is important because two groups of individuals are heavily exposed to high-LET radiation during their careers, warranting consideration for genetic risk assessment. First, on intercontinental flights, at altitudes around 10,000–12,000 meters, the estimated mean cumulative exposure for civil aviation air crew is 3 mSv per year, with a range from 1 to 10 mSv per year. The degree of exposure varies according to the altitude, latitude, and solar activity. Therefore, air crew members who cruise on long intercontinental flights are exposed more than air crew members of domestic flights (Bagshaw et al., 1996). More than 50% of the effective dose present at the altitudes used for commercial intercontinental civil flying comes from irradiation due to secondary neutrons (De Angelis et al., 2001, Grajewski et al., 2002, Langner et al., 2004, Tveten et al., 2000). Second, it is well known that during space flights astronauts are exposed to a complex radiation environment consisting of 87% high-energy protons, 11% helium ions and 2% heavy charged ions, as well as being exposed to secondary radiation including neutrons. During long-term interplanetary missions, such as travel to Mars or into deeper space, it is expected that astronaut crews will accumulate doses of radiation of around 1 Sv or higher (Antipov et al., 1994, De Angelis et al., 2004, Petrov, 2004, Wilson et al., 2004, Zeitlin et al., 2004). During their careers, members of both flight crews and astronaut crews could accumulate significantly higher radiation doses than members of other occupations exposed to ionizing radiation. Currently, a high priority is understanding the risk of the later effects from exposure to GCR-galactic cosmic radiation and SPE-solar particle events, such as cataracts, cancer, neurological disorders and hereditary effects (Cavallo et al., 2002, Durante et al., 2003, Fedorenko et al., 2000, Fedorenko et al., 2001, Langner et al., 2004, Heimers, 2000, Nicholas et al., 2003, Picco et al., 2000, Romano et al., 1997, Testard and Sabatier, 1999). Most of our knowledge of the genetic effects of exposure to heavy charged particles comes from either accelerator-based experiments or radiobiological studies conducted directly in space. The latter have the advantage of including interaction of all other space environmental factors, but are very expensive.

Our experience from comparative studies involving a variety of mammalian species subjected to acute photon irradiation indicates that the rat is most similar to man in genetic susceptibility (Vaglenov, 1985). Therefore, we extended our research program to compare the mouse and the rat in order to ascertain the genetic effects of exposure to protons and heavy charged particles, using the same radiation conditions on each species as a base for further risk assessment. Additionally, in this report we present the RBE of 1.5 MeV acute neutron exposure on mice spermatogonia.