Induction of specific-locus and dominant lethal mutations in male mice by n-propyl and isopropyl methanesulfonate

Abstract

n-Propyl methanesulfonate (nPMS) and isopropyl methanesulfonate (iPMS) induce dominant lethal and specific-locus mutations in male mice. The responses of the various spermatogenic stages to the induction of mutations differ markedly for nPMS and iPMS. Independent of the effective dose range the induction of dominant lethal mutations by nPMS is limited to spermatozoa and spermatids. In contrast, the induction of dominant lethal mutations by iPMS is dose dependent: a dose of 20 mg iPMS/kg body weight (bw) is active only in spermatocytes, while a dose of 100 mg/kg bw induces dominant lethal mutations in all postspermatogonial germ cell stages. One other striking difference in the biological effectiveness of both compounds is that iPMS induces a sterile phase in stem-cell spermatogonia, wheras nPMS treated males even at the highest dose are fully fertile.