Induction of hprt mutations in mice after exposure to fission-spectrum neutrons or 60Co gamma rays.

The effects of exposure to fission-spectrum neutrons and 60Co gamma rays on mutation induction in B6CF1 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 x 10(4) feeder cells (syngeneic lymphocytes irradiated with 50 Gy gamma rays). The selective agent used as 6-thioguanine at a concentration of 2.5 micrograms/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 x 6, total 1.5 Gy) or photons (1.5 Gy x 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 60Co photons was approximately the same, i.e., 5.98 x 10(-5) +/- 1.51 x 10(-5) (SE) vs. 5.56 x 10(-5) +/- 3.09 x 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 x 10(-5) +/- 5.39 x 10(-5) (SE), total dose 1.5 Gy, vs 2.30 x 10(-5) +/- 9.07 x 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 60Co gamma rays increase when the comparisons are made between fractionated rather than single-dose exposure regimens.