Mouse spermatogonia and spermatocyte sensitivity to chemical mutagens.

Twenty-one chemicals have been tested for the induction of chromatid aberrations in differentiating spermatogonia, and 14 of them gave a positive response. However, when spermatocytes derived from treated As-spermatogonia were analyzed for reciprocal translocations, the results were negative for 10 out of 17 chemicals tested. For the remaining 7 chemicals, either conflicting results or no dose dependency has been reported. The difference between aberrations in differentiating spermatogonia and the lack of translocations in spermatocytes after treatment of stem-cell spermatogonia was most obvious with mitomycin C. Reasons for this difference are discussed. In meiotic prophase, mitomycin C and TEM caused aberrations observable at diakinesis only after treatment of spermatocytes in S-phase. In contrast, ionizing radiation produces its main effect during pachytene. Translocation heterozygotes were recovered among progeny of mitomycin C- and TEM-treated spermatocytes. Conclusions for human health hazards are: (1) chromosomal aberrations induced by chemical mutagens in spermatogonia do not pose a considerable risk because they do not sufficiently survive germinal selection; (2) chemical treatment of spermatocytes can result in chromosomally abnormal offspring. The quantification of human ill health based on translocation yields obtained in animal experiments poses great difficulties that have not been resolved.