Bleomycin, unlike other male-mouse mutagens, is most effective in spermatogonia, inducing primarily deletions

Dominant-lethal tests [P.D. Sudman, J,C. Rutledge, J.B. Bishop, W.M. Genero so, Bleomycin: female-specific dominant lethal effects in mice, Mutat. Res. 296 (1992) 205-217] had suggested that Bleomycin sulfate (Blenoxane), BLM, might be a female-specific mutagen. While confirming that BLM is indeed a powerful inducer of dominant-lethal mutations in females that fails to indu ce such mutations in postspermatogonial stages of males, we have shown in a specific-locus test that BLM is, in fact, mutagenic in males. This mutagen icity, however, is restricted to spermatogonia (stem-cell and differentiati ng stages), fur which the specific-locus mutation rate differed significant ly (P < 0.008) from the historical control rate. In treated groups, dominan t mutations, also, originated only in spermatogonia. With regard to mutatio n frequencies, this germ-cell-stage pattern is different from that for radi ation and fur any other chemical studied to date, except ethylnitrosourea ( ENU). However, the nature of the spermatogonial specific-locus mutations di fferentiates BLM from ENU as well, because BLM induced primarily (or, perha ps, exclusively) multilocus deletions. Heretofore, no chemical that induced specific-locus mutations in spermatogonia did not also induce specific-loc us as well as dominant-lethal mutations in postspermatogonial stages, makin g the dominant lethal test, up till now, predictive of male mutagenicity in general. The BLM results now demonstrate that there are chemicals that can induce specific-locus mutations in spermatogonia without testing positive in postspermatogonial stages. Thus, BLM, while not female-specific, is uniq ue, (a) in its germ-cell-stage specificity in males, and (b) in inducing a type of mutation (deletions) that is atypical for the responding germ-cell stages (spermatogonia). (C) 2000 Elsevier Science B.V. All rights reserved.