Differential spermatogenic response of mice to the induction of mutations by antineoplastic drugs

Abstract

Summary 2,2′-Dichloro- N -methyldiethylamine- N -oxide (DMO) induced dominant lethal mutations in mice exclusively in spermatozoa. Spermatozoa were not affected by N -isopropyl-α-(2-methylhydrazino)- p -toluamide (IMT). IMT induced dominant lethal mutations in mice in spermatids and spermatocytes. IMT also affected the development of spermatocytes and spermatogonia. Mitomycin C (MC) significantly increased the frequency of specific locus mutations in spermatogonia of mice but not in postspermatogonial germ-cell stages. The differential spermatogonic response of mice to the induction of mutations is very likely due to the different mode of action of the chemical mutagens and their distinct effects on the structural and macromolecular changes during the development of the germ cells. The germ-cell stage-specific induction of mutations is an important clue for the evaluation of genetic risks of antineoplastic drugs.