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Mutagenesis vol. 13 no. 6 pp. 607-612, 1998
© 1998 UK Environmental Mutagen Society/Oxford University Press

research-article

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

Katharine P. Hoyes1, Pamela J. Wadeson, Harbans L. Sharma, Jolyon H. Hendry and Ian D. Morris

School of Biological Sciences and Department of Medical Biophysics, University of Manchester Manchester Cancer Research Campaign Section of Genome Damage and Repair, Paterson Institute for Cancer Research Manchester, UK

We have used the Big Blue® lacI transgenic mouse reporter system to investigate mutation induction in the testes, spleen and liver after exposure to an internally incorporated radionuclide, 114mIn, whole body irradiation with 60Co {gamma}-rays and systemically administered cyclophosphamide. Spontaneous mutation frequencies were 6–17x10–6. 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 ~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 ~2.5- fold after systemic administration of 114mIn and 4.5-fold after 1 Gy 60Co {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 lacI 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 lacI transgene.

1To whom correspondence should be addressed at: CRC Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. Tel: +44 161 446 3133; Fax: +44 161 446 3109; Email: khoyes{at}picr.man.ac.uk


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