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

• Published in: Mutagenesis Vol. 13; no. 6; pp. 607 - 612
• Main Authors: Hoyes, Katharine P., Wadeson, Pamela J., Sharma, Harbans L., Hendry, Jolyon H., Morris, Ian D.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-11-1998
• Subjects: Animals; Bacterial Proteins - drug effects; Bacterial Proteins - genetics; Bacterial Proteins - radiation effects; Biological and medical sciences; Chemical mutagenesis; Cyclophosphamide - toxicity; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Escherichia coli Proteins; Indium Radioisotopes; Lac Repressors; Liver - drug effects; Liver - radiation effects; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutagenicity Tests - methods; Mutagens - toxicity; Mutation; Repressor Proteins - drug effects; Repressor Proteins - genetics; Repressor Proteins - radiation effects; Spleen - drug effects; Spleen - radiation effects; Testis - drug effects; Testis - radiation effects; Toxicology; Antineoplastic agent; Mutagenicity testing; Toxicity; Rodentia; Transgenic animal; Tissue specificity; Alkylating agent; Ionizing irradiation; Vertebrata; Cyclophosphamide; Gamma irradiation; Mammalia; Mouse; Nitrogen mustard; Mutation
• ISSN: 0267-8357; 1464-3804
• DOI: 10.1093/mutage/13.6.607

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 γ-rays and systemically administered cyclophosphamide. Spontaneous mutation frequencies were 6−17×10−6. 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 ∼1.5-fold) after exposure to 1 Gy γ-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 γ-rays. When data from all organs were pooled, mutation frequency was doubled after exposure to 1 Gy γ-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.