Mutagenesis in Mammalian Germs Cells by Radiation or Nitrogen Mustard—A Comparative Study
The dominant lethal mutant rate was determined in mouse embryos fertilized by spermatozoa that were derived from spermatogonia treated with nitrogen mustard, gamma radiation or accelerated neon ions. The doses chosen (2.0 mg/kg nitrogen mustard, 1.8 Gy 137Cs and 0.65 Gy neon) gave an isoeffect when the dominant lethal mutant rate was evaluated in embryos fertilized by spermatozoa that were treated in the sensitive spermatid stage.
An in vitro methodology was employed. Male mice were mated 35 or more days after treatment. The 2-cell stage embryos were removed from the female and cultured for a total of 7 days during which time they develop to an early postimplantation stage. The frequency of successful development to the trophectoderm outgrowth stage was used as the index of mutation induction.
Although each treatment gave essentially the same mutant rate in treated spermatids, the mutant rate in treated spermatogonia seemed to be different. These rates were 1.5% for cesium, −2.7% for neon, and 8.3% for nitrogen mustard. Although none of these rates were significantly different than controls, other data suggest that neon and nitrogen mustard do induce dominant lethal mutations in spermatogonia. When a higher dose of neon was tested, the dominant lethal rate increased to 19%. When a more sensitive endpoint (the frequency of inner cell mass differentiation) was used to evaluate nitrogen mustard induced mutations, a rate of 11% was found. Both these rates are significant.
These results indicate that the in vitro method can detect mutagenesis by drugs or radiation at clinically relevant doses.
KeywordsMutation Induction Nitrogen Mustard Spermatogonial Stem Cell Ethyl Methane Sulfonate Dominant Lethality
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