Antimutagenic Effects of Radioprotector WR-2721 Against Fission-spectrum Neutrons and ⁶⁰Co γ-rays in Mice

Abstract

The antimutagenic effects of the radiation protective agent, S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721), were studied against fission-spectrum-neutron- and ⁶⁰Co-γ-ray-induced mutagenesis in mice. Mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus was measured 56 days following whole-body irradiation with JANUS neutrons (single doses, 50–150 cGy) or ⁶⁰Co photons (single doses, 250–750 cGy). Splenic T lymphocytes from B6CF₁ mice were grown in round-bottomed 96-microwell culture plates with or without the selective agent 6-thioguanine (6-TG). The mutant frequency, as a result of exposure to neutrons or ⁶⁰Co photons, increased 100-fold with dose. Doses of 150 cGy neutrons and 750 cGy ⁶⁰Co photons were euqally mutagenic. When animals were injected with WR-2721 at a dose of 400 mg/kg body weight, i.p., 30 min before whole-body irradiation with JANUS neutrons or ⁶⁰Co photons, mutant frequencies were significantly reduced at all radiation doses (i.e. protection factors of 1·4 and 2·4, respectively). Thus, the aminothiols are effective antimutagens. A novel clinical application of these compounds could be in their use to protect against radiation- and/or chemotherapy-induced genotoxic damage to normal cells.