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Published on: December 28, 2021
Aberration induction by mitomycin C in early primary spermatocytes of mice
1Abteilung für Genetik, Institut für Biologie, Gesellschaft für Strahlen- und Unweltforschung, Neuherberg bei München, Germany.
Abstract:
MC is well known to induce dominant lethal mutations in mouse spermatocytes. Tests were done to determine whether chromosomal aberrations could be identified in spermatocytes as being responsible for the dominant lethal effects. Male mice were treated with single doses of MC during DNA synthesis preceding meiosis and during early prophase of meiosis. Simultaneous labeling was performed to identify cells that were in S-phase during the time of treatment. Diakineses-metaphases I were analyzed for the occurrence of univalents, gaps, fragments and rearrangements. The frequencies of cells with aberrations increased with dose and time after treatment. Maximal values were obtained after 12 days, indicating that MC was most effective in cells undergoing DNA replication. 95% of these cells were labeled. The majority of aberrant cells contained one or more fragments. These cells will lead to dominant lethality of the zygotes after fertilization. Cells with rearrangements occurred 11 and 12 days after treatment. These cells can develop into sperm carrying a reciprocal translocation which would then give rise to semi-sterile progeny after fertilization. Further investigations are needed to study the transmission of rearrangements observed in primary spermatocytes.
Insights
Mustard gas (MC) causes dominant lethal mutations in mouse sperm by inducing chromosomal aberrations. These DNA damages, particularly fragments, lead to zygote lethality, while rearrangements can cause semi-sterile offspring.
Area of Science:
- Genetics
- Toxicology
- Reproductive Biology
Background:
- Mustard gas (MC) is a known mutagen that induces dominant lethal mutations in mouse spermatocytes.
- The specific chromosomal aberrations responsible for these dominant lethal effects require identification.
Purpose of the Study:
- To investigate chromosomal aberrations in mouse spermatocytes induced by mustard gas (MC).
- To correlate these aberrations with dominant lethal effects and potential heritable genetic damage.
Main Methods:
- Male mice were administered single doses of MC during DNA synthesis (S-phase) and early meiotic prophase.
- Simultaneous labeling identified cells in S-phase during treatment.
- Diakinesis-metaphase I spermatocytes were analyzed for chromosomal aberrations (univalents, gaps, fragments, rearrangements).
Main Results:
- Frequencies of chromosomal aberrations increased with MC dose and time post-treatment, peaking at 12 days.
- MC was most effective in cells undergoing DNA replication (95% labeled).
- Aberrant cells predominantly contained fragments, leading to zygote lethality; rearrangements were observed later, potentially causing semi-sterility.
Conclusions:
- Mustard gas (MC) induces dominant lethality via chromosomal fragments in spermatocytes, particularly affecting cells in DNA synthesis.
- MC can also induce rearrangements in later spermatocyte stages, potentially leading to heritable semi-sterility.
- Further research is needed to confirm the transmission of MC-induced rearrangements.
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