Induction of hprt Mutations in Mice after Exposure to Fission-Spectrum Neutrons or 60 Co Gamma Rays

The effects of exposure to fission-spectrum neutrons and 60 Co γ rays on mutation induction in ${\rm B}6{\rm CF}_{1}$ mice were investigated. Mutation induction was measured at the hypoxanthine-phosphoribosyl-transferase (hprt) locus in splenic lymphocytes at 56 days after whole-body irradiation. Lymphocytes were cultured 12-16 days in round-bottomed, 96-microwell plates in the presence of 5× 104 feeder cells (syngeneic lymphocytes irradiated with 50 Gy γ rays). The selective agent used was 6-thioguanine at a concentration of 2.5 μg/ml. Animals were exposed to either single doses of neutrons (1.5 Gy) or photons (7.5 Gy) or fractionated doses delivered over 2 weeks of neutrons (0.25 Gy × 6, total 1.5 Gy) or photons (1.5 Gy × 6, total 9.0 Gy). The frequency of hprt mutant induction by fission-spectrum neutrons delivered in a 1.5-Gy single dose compared to a 7.5-Gy single dose of 60 Co photons was approximately the same, i.e., $5.98\times 10^{-5}\pm 1.51\times 10^{-5}$ (SE) vs. $5.56\times 10^{-5}\pm 3.09\times 10^{-5}$ (SE), respectively (Student's two-tailed t test, P = 0.8997). Multiple doses of neutrons gave rise to slightly higher mutant frequencies compared to photons even though the ratio of total doses of neutrons to photons was increased from 5 to 6, i.e., $8.71\times 10^{-5}\pm 5.39\times 10^{-5}$ (SE), total dose 1.5 Gy, vs $2.30\times 10^{-5}\pm 9.07\times 10^{-6}$ (SE), total dose 9.0 Gy, respectively (Student's two-tailed t test, P = 0.3330). These results suggest that the relative differences in magnitude in radiation-induced genotoxic effects between fission-spectrum neutrons and 60 Co γ rays increase when the comparisons are made between fractionated rather than single-dose exposure regimens.