M. Katoh et al., STUDIES ON MUTATIONS IN MALE GERM-CELLS OF TRANSGENIC MICE FOLLOWING EXPOSURE TO ISOPROPYL METHANESULFONATE, ETHYLNITROSOUREA OR X-RAY, Mutation research. Genetic toxicology testing, 341(1), 1994, pp. 17-25
Transgenic mice have recently been used for mutagenesis assays in vivo
. The present study was undertaken to clarify whether such assays can
detect mutations induced after treatment of male germ cells in mouse w
ith isopropyl methanesulfonate (iPMS), ethylnitrosourea (ENU) or X-ray
irradiation. The transgenic mice used for assay are Muta(TM) Mouse (M
M) strain, which carries 80 copies of the bacterial lacZ gene per cell
as targets for mutagenesis. Male MM animals were given a single intra
peritoneal injection of 200 mg/kg iPMS, 150 mg/kg ENU or were irradiat
ed with 500 rads of X-rays. Vasa deferential sperm, caudal epididymal
sperm and/or whole testes were extracted at various times after treatm
ent with each agent. After the genomic DNA was extracted from each tis
sue, mutation analysis at the lacZ locus was carried out by the method
of Myhr et al. The spontaneous lacZ(-) mutant frequencies were on the
order of 10(-5)-10(-6). The lacZ(-) mutant frequencies in all treatme
nt groups were increased over the control animals. The iPMS-induced mu
tant frequency in postmeiotic stages was low. However, ENU induced rel
atively high mutant frequencies in the spermatogonia. X-rays induced m
utant frequencies in the late spermatid and early spermatid stages tha
t were higher than the mutant frequencies in spermatogonia. Mutant fre
quencies in MM detected after treatment of male germ cells with ENU or
X-rays were lower than mutant frequencies detected by the mouse speci
fic-locus test in previous reports. Hence, considering the lower resol
ution power of the transgenic animal mutagenesis assays using the targ
et lacZ gene compared with the specific locus test, to detect mutation
s induced in male germ cells, it is not clear whether this assay is a
practical alternative to the specific locus test.