Effects of Mitomycin-C on Spermatogenesis of Mice with Reference to the Dose Relation between Mitomycin-C and X-rays

Abstract

The damage to spermatogenetic cells of mice following the application of Mitomycin-C (1.7 or 3.4mg/kg) was studied on some quantitative and histological bases with particular attention to the sensitivity of spermatogenetic cells of each population, and the results obtained were compared with those from X-ray-irradiated mice.
A remarkable decrease of spermatogonia, spermatocytes, spermatids and spermatozoa occurs in the order of their developmental stages at the 1st, 2nd, 3rd and 4th week after the treatment. Evidence presented implies that the sensitivity of spermatogenetic cells to the drug differs by their developmental stages.
The decrease of these cell types was more marked with the increased concentration of the drug. Their return to the control value in the 3.4mg/kg case is one week later than that in the 1.7mg/kg case.
It has been shown that spermatogonia are more sensitive than germ cells of other types, and that type B spermatogonia are higher in sensitivity than type A spermatogonia.
Spermatocytes show necrosis at the resting stage as well as in the process of division and chromosome aberrations at metaphase and anaphase. Evidence is available to show that some spermatocytes seem to participate in the formation of abnormal spermatids and spermatozoa, or otherwise, slough in the ductus epididymidis.
No pathological changes were observed to occur in spermatids and spermatozoa treated with the drug. Their depletion seems to be attributable to the obstruction of spermatogenesis due to the disappearance of spermatogonia.
Sertoli cells and interstitial cells show a gradual increase following the application of the drug suggesting a correlation with the shrinkage of seminiferous tubules.
The rate in decrease of the testis-weight after the treatment with the drug is more marked than that of the tubule-diameter. Further, the features involving decrease and recovery of the testis-weight and the tubule-diameter can be explained on the basis of the destruction and recovery of spermatogenetic cells.
Data so far presented make it possible to conclude that Mitomycin-C and X-rays seem to affect male germ cells leading to their ultimate damage in a generally similar manner. The relative dosage between Mitomycin-C and X-rays considered on the basis of disappearance and recovery rate of spermatogonia seems to be as follows: 1.7mg/kg of Mitomycin-C corresponds approximately to the dose of 300r of X-rays and 3.4mg/kg to the dose of 500r.