Effects of WR-1065 and WR-151326 on Survival and Neoplastic Transformation in C3H/10T½ Cells Exposed to TRIGA or JANUS Fission Neutrons

Abstract

We demonstrated the ability of aminothiols WR-1065 and WR-151326, each at concentration 1 mM, to protect C3H/10T½ cells against the transforming effects of fission neutrons under two distinct sets of experimental conditions. Experiments with WR-1065 were performed with stationary cultures of C3H/10T½ cells, and a TRIGA reactor-generated fission neutron field at the Armed Forces Radiobiology Research Institute (USA). Experiments with WR-151326 were performed with proliferating cultures of C3H/10T½ cells and a JANUS reactor-generated fission neutron field at the Argonne National Laboratory (USA). Radioprotectors were present before, during, and after irradiation for total periods of 35 min (WR-151326; 10 min pre-incubation) or 1 h (WR-1065; 30 min pre-incubation). Bioavailability of WR-1065 and WR-151326 in extracellular medium under experimental conditions simulating those of the transformation experiments was studied by measuring oxidation rates in the presence of attached C3H/10T½ cells in plateau and exponential phase of growth for periods of up to 5 h. Estimated half-lives for autoxidation of WR-1065 or WR-151326 were approximately 8 min or 1 h regardless of the proliferative status of cells. In the absence of WR-compounds, dose-response data for transformation induction by neutrons from TRIGA and JANUS reactors were fitted to a common curve with a linear coefficient of about 7 × 10⁻⁴/Gy. WR-151326 and WR-1065 were found to provide significant radioprotection by factors of 1·79 ± 0·08 and 3·23 ± 0·19, respectively, against fission neutron-induced neoplastic transformation. No significant protection against neutron-induced cell lethality was observed.