Mutation studies in lacI transgenic mice after exposure to radiation or cyclophosphamide

We have used the Big Blue(R) lacI transgenic mouse reporter system to investigate mutation induction in the testes, spleen and liver after exposure to an internally incorporated radionuclide, In-114m, whole body irradiation with Co-60 gamma-rays and systemically administered cyclophosphamide. Spontaneous mutation frequencies were 6-17 x 10(-6). No statistically significant mutation induction was observed in testes or spleen at 35 days after exposure to any test agent, although mutation frequencies tended to be increased (by similar to 1.5-fold) after exposure to 1 Gy gamma-rays. However, liver mutation frequencies were doubled after treatment with 100 mg/kg cyclophosphamide and were elevated by similar to 2.5-fold after systemic administration of In-114m and 4.5-fold after 1 Gy Co-60 gamma-rays. When data from all organs were pooled, mutation frequency was doubled after exposure to 1 Gy gamma-rays, but no other significant increases were observed. These findings support the hypothesis that the lac1 transgenic mouse may be relatively inefficient at detecting mutations induced by exposure to ionizing radiation or other agents which produce a spectrum of deletion sizes, including those which are larger than the lac1 transgene.