Dose-dependent induction of recessive mutations with N-ethyl-N-nitrosourea in primordial germ cells of male mice.
Using a specific locus test, we previously found that N-ethyl-N-nitrosourea (ENU) induces recessive mutations at a relatively high rate in male mouse primordial germ cells (PGC) at 8.5, 10.5 and 13.5 days of development (G8.5, G10.5 and G13.5). A large difference was observed on the induced mutation rate between 30 and 50 mg/kg ENU in 10.5-day PGC. We therefore carried out specific locus tests to ascertain whether ENU induces recessive mutations in a dose-dependent manner in G8.5 and G10.5 PGC. We also gave multiple doses of 25 mg/kg ENU using an 18-h interval, the approximate doubling time of PGC at these developmental stages, to test for an additive effect on the induced mutations rate. A dose-dependent induction of recessive mutations by ENU was observed in both G8.5 and G10.5 PGC, and multiple dosing of 25 mg/kg ENU showed an additive effect. Comparing these results to data on spermatogonial stem cells, we conclude the capacity to repair ENU-induced premutagenic damages is less effective in male mouse PGC at these developmental stages than in spermatogonial stem cells.
Shibuya
T
T
Laboratory of Genetic Toxicology, Hatano Research Institute, Food and Drug Safety Center, Kanagawa, Japan.
Horiya
N
N
Matsuda
H
H
Sakamoto
K
K
Hara
T
T
D000818:Animals; D002455:Cell Division; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D005038:Ethylnitrosourea / Q000008:administration & dosage*; D005260:Female; D005298:Fertility / Q000187:drug effects; D005808:Genes, Recessive; D005854:Germ Cells; D008297:Male; D008540:Meiosis / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D016296:Mutagenesis / Q000187:drug effects; D009153:Mutagens / Q000008:administration & dosage*
D009153:Mutagens; D005038:Ethylnitrosourea