An examination of respiratory distress and chromosomal abnormalities in the offspring of male mice treated with ethylnitrosourea.
A functional defect (respiratory distress), in addition to morphological defects, was induced in the offspring of male ICR mice treated with ethylnitrosourea (ENU) before mating. ENU (100 and 50 micrograms/g) was injected intraperitoneally into adult male ICR mice that were then mated with untreated females. After the cesarian operation on the 18th day of gestation, fetuses were resuscitated. In the apneic fetuses showing respiratory distress, the lung was collapsed and the ductus arteriosus was not closed. The incidence of fetuses showing respiratory distress was significantly increased with the high dose (100 micrograms/g) of ENU, and it was higher after spermatogonial exposure than after postmeiotic exposure. There was no linearity in the dose-response relationship at the lower dose (50 micrograms/g), as was the case with the specific-locus mutation. The frequency per microgram ENU of fetuses showing respiratory distress was 3.7 X 10(-4) for spermatogonial treatment (calculated at a dose of 100 micrograms/g), the value being about 10-20 times higher than that of ordinary mutations in mice. About half of the fetuses showing respiratory distress often had specific anomalies (dwarfism and gigantic thymus), but the remainder showed no morphological changes. Spermatogonial treatment produced a zero or very low incidence of translocations in the meiotic configurations of primary spermatocytes. G-band analysis of the affected F1 fetuses also revealed no visible chromosomal abnormalities (there could be small deletions or inversions) except that trisomy 19 was found in a dwarf fetus.
Nomura
T
T
Department of Radiation Biology, Faculty of Medicine, Osaka University, Japan.
Gotoh
H
H
Namba
T
T
D000014:Abnormalities, Drug-Induced; D000818:Animals; D002869:Chromosome Aberrations; D005038:Ethylnitrosourea; D007621:Karyotyping; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009154:Mutation; D012131:Respiratory Insufficiency / Q000139:chemically induced / Q000235:genetics*; D013093:Spermatogonia / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects*
D005038:Ethylnitrosourea