Mutant Frequencies in lacZ Transgenic Mice following the Internal Irradiation from 89Sr or the External γ-Ray Irradiation

Abstract

Mutagenesis assays using transgenic mice have been recently developed and applied to the studies on the mutagenesis. The present study was undertaken to clarify whether the mutagenesis assay with transgenic mice could detect the mutations induced by the internal β-ray irradiation from 89Sr or the external γ-ray irradiation. The transgenic mice used were Muta™ mouse strain, which carries 80 copies of the bacterial lacZ gene per cell as a target of mutagenesis. Female animals were given intraperitoneal injections of ethylnitrosourea (50 mg/kg per day) for five days, a single intravenous injection of 89Sr (7.4 and 74 MBq/kg), or daily irradiation with 1.5 Gy γ-rays for five days. The liver, spleen, and bone marrow were collected 15 days after the treatment with each agent. After the genomic DNA was extracted from each tissue, mutation analysis at lacZ locus was carried out. The spontaneous lacZ mutant frequencies were 2-4 × 10-5. The frequencies of mutants induced by ethylnitrosourea in the liver, spleen and bone marrow were 68, 55, and 11 × 10-5, respectively. In contrast, the mutant frequencies detected after the treatment with γ-rays were not so high in all three tissues as those treated with ethylnitrosourea. The injection of 89Sr at a dose of 74 MBq/kg induced mutation at significantly higher frequencies in the bone marrow, but not in the liver and spleen. The results clearly showed that the mutation assay system used here could detect mutagenic effects of the local irradiation from 89Sr, but was relatively insensitive to the β- and γ-ray irradiation compared with the chemical mutagens such as ethylnitrosourea.