We have used the Big Blue(R) lacI transgenic mouse reporter system to
investigate mutation induction in the testes, spleen and liver after e
xposure to an internally incorporated radionuclide, In-114m, whole bod
y irradiation with Co-60 gamma-rays and systemically administered cycl
ophosphamide. 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 exp
osure to 1 Gy gamma-rays. However, liver mutation frequencies were dou
bled 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 po
oled, mutation frequency was doubled after exposure to 1 Gy gamma-rays
, but no other significant increases were observed. These findings sup
port the hypothesis that the lac1 transgenic mouse may be relatively i
nefficient at detecting mutations induced by exposure to ionizing radi
ation or other agents which produce a spectrum of deletion sizes, incl
uding those which are larger than the lac1 transgene.