The induction of dominant lethal mutations in rats by alkane sulphonic esters

Sterility resulting from treatment of male rats with methyl ethane sulphonate and ethyl methane sulphonate was found to be due to the induction of dominant lethal mutations in spermatozoa and spermatids. Spermatids in the acrosome phase of development were found to be the most sensitive cells and at low doses of both compounds the majority of deaths occurred after implantation. The earlier cell stages, i.e. spermatogenia and spermatocytes, were the most sensitive to isopropyl methane sulphonate and Busulphan (Myleran). The action on spermatogonia was confirmed by spermatid counts and the time of occurrence of oligospermia or aspermia was calculated. Pre-implantation deaths occurred mainly in the early cleavage stages after both isopropyl methane sulphonate and Busulphan; at least part of these losses can be attributed to the induction of dominant lethal mutations in spermatocytes and early spermatids. Isopropyl methane sulphonate appears to be the more effective of the two drugs in this respect.