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Detection of mitomycin C-induced testicular toxicity by micronucleus assay in mice

Soichi Nakagawa1,2, Chisato Mori1,3

  • 1Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba.

Reproductive Medicine and Biology
|April 28, 2018
PubMed

Insights

Mitomycin C induces male germ cell apoptosis by causing DNA damage and chromosomal aberrations in mouse spermatogonia and spermatocytes. This study links chromosomal damage to apoptosis, suggesting a mechanism for eliminating damaged cells.

Area of Science:

  • Reproductive biology
  • Toxicology
  • Genetics

Background:

  • Mitomycin C is a cancer therapeutic agent known to inhibit DNA synthesis.
  • Previous research indicated Mitomycin C induces apoptosis in mouse spermatogenic cells.
  • Apoptotic cell death was predominantly observed in spermatogonia and less in spermatocytes.

Purpose of the Study:

  • To investigate the mechanism by which Mitomycin C induces spermatogenic cell apoptosis.
  • To determine if DNA damage or chromosomal aberrations are responsible for Mitomycin C-induced apoptosis.
  • To test the hypothesis that Mitomycin C eliminates male germ cells with DNA damage.

Main Methods:

  • Utilized TdT-mediated dUTP-biotin nick-end labeling to identify apoptotic cells.
  • Employed a micronucleus assay to detect chromosomal damage in spermatogonia and spermatocytes.
  • Compared the frequency of micronuclei at different stages of spermatogenesis.

Main Results:

  • Mitomycin C treatment significantly increased the frequency of micronuclei in mouse testes.
  • Higher numbers of micronuclei were observed in spermatogonia and early spermatocytes compared to secondary spermatocytes.
  • Apoptosis and chromosomal aberrations occurred concurrently in spermatogonia and spermatocytes.

Conclusions:

  • Mitomycin C induces chromosomal aberrations in spermatogenic cells.
  • Chromosomal aberrations in spermatogenic cells likely trigger apoptosis.
  • This suggests a cellular mechanism for removing male germ cells with DNA damage induced by Mitomycin C.
Keywords:
testisacridinemicemicronucleusmitomycin C

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