Genotoxic potency in mouse spermatogonial stem cells of triethylenemelamine, mitomycin C, ethylnitrosourea, procarbazine, and propyl methanesulfonate as measured by F1 congenital defects.
Male ICR mice were intraperitoneally injected with TEM, MMC, ENU, PCZ, or PMS and mated to untreated females of the same strain on days 64-80 after the treatment. Copulations during this period involve sperm that were spermatogonial stem cells at the time of the treatment. The fetuses were examined on day 18 of pregnancy for external and skeletal abnormalities. The 5 mutagens tested all caused significant increases in the incidence of abnormal fetuses over the control level. The genotoxically effective dose, in mmole/kg, for producing fetal abnormalities with a frequency of 2% was estimated to be 0.007 for TEM and MMC, 0.6 for ENU, 1.8 for PCZ, and 3.0 for PMS. These values correlate well with the mutagenic potency estimated from the data reported for inducing specific-locus mutations in spermatogonial stem cells. Irrespective of the kind of mutagen used, external abnormalities represented by cleft palate and dwarfism occurred more frequently than skeletal abnormalities represented by rib malformations. It is concluded from these data that F1 fetal abnormalities can serve as sensitive indicators for quantitatively assessing the genotoxicity of a chemical agent in spermatogonial stem cells.
Nagao
T
T
Hatano Research Institute, Food and Drug Safety Center, Kanagawa, Japan.
Fujikawa
K
K
D000014:Abnormalities, Drug-Induced; D000818:Animals; D005038:Ethylnitrosourea / Q000633:toxicity*; D008297:Male; D008698:Mesylates / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D016685:Mitomycin; D008937:Mitomycins / Q000633:toxicity*; D009152:Mutagenicity Tests; D011344:Procarbazine / Q000633:toxicity*; D013093:Spermatogonia / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects*; D014265:Triethylenemelamine / Q000633:toxicity*
D008698:Mesylates; D008937:Mitomycins; D011344:Procarbazine; D016685:Mitomycin; C046861:n-propyl methane sulfonate; D014265:Triethylenemelamine; D005038:Ethylnitrosourea