Skip to main content

Advertisement

SpringerLink
Log in

Estimation of the frequencies of induced mutations in spermatogenic cells of senescence-accelerated prone mice of the SAMP1 strain

  • Animal Genetics
  • Published:
Russian Journal of Genetics Aims and scope Submit manuscript

Abstract

The results obtained in this work demonstrate the dynamics of cytogenetic changes of spermatogenic cells in senescence-accelerated prone mice, strain SAMP1, after a single exposure to a chemical mutagen, dipin, at a genetically active dose of 30 mg/kg. In the time interval between days 3 and 28 the frequency of induced spermatogonial micronuclei does not significantly exceed the level of spontaneous mutagenesis. The lack of an experimental effect of micronuclei in this time interval is probably a consequence of mitotic delay and (or) of the death of a considerable part of genetically defective cells in the spermatogonial compartment. Different stages of meiosis exhibit different chemical sensibilities: the yield of round spermatids with micronuclei is maximum after treatment of early primary spermatocytes (preleptotene-leptotene stage) with dipin. The high sensibility of preleptotene and leptotene spermatocytes is confirmed by the sperm head shape abnormality assay. Chromosome damage caused by dipin in spermatogonial stem cells is irreversible, as evidenced by a sharp increase in the frequencies of spermatogonial and meiotic micronuclear aberrations within long periods after treatment. Increased genetic instability in the stem compartment does not lead to irreversible degradation of the system of development of male sex cells in senescence-accelerated SAMP1 mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Takeda, T., Hosokawa, M., Takeshita, S., et al., A New Murine Model of Accelerated Senescence, Mech. Aging Dev., 1981, vol. 17, pp. 183–194.

    Article  PubMed  CAS  Google Scholar 

  2. Takeda, T., Hosokawa, M., and Huguchi, K., Senescence-Accelerated Mouse (SAM): A Novel Murine Model of Aging, The SAM Model of Senescence, Takeda, T., Ed., Amsterdam: Excerpta Medica, 1994, pp. 15–22.

    Google Scholar 

  3. Nisitani, S., Hosokawa, M., Sasaki, M.S., et al., Acceleration of Chromosome Aberrations in Senescence-Accelerated Strains of Mice, Mutat. Res., 1990, vol. 237, nos. 5–6, pp. 221–228.

    PubMed  CAS  Google Scholar 

  4. Lee, D.W., Sohn, H.O., Lira, H.B., et al., Comparison of Sister Chromatid Exchange Rates in Bone Marrow Cells of SAMRI and SAMPI with Age and Effect of Korean Ginseng Extract on Sister Chromatid Exchange Rate, The SAM Model of Senescence, Takeda, T., Ed., Amsterdam: Excerpta Medica, 1994, pp. 129–131.

    Google Scholar 

  5. Tobita, M., Nakamura, S., Nagano, I., et al., DNA Single-Strand Breaks in Hippocampal Regions of Senescence Accelerated Mice (SAMP8/Ta) Detected by Modified in situ Nick Translation Procedure, The SAM Model of Senescence, Takeda, T., Ed., Amsterdam: Excerpta Medica, 1994, pp. 125–128.

    Google Scholar 

  6. Odagiri, Y., Uchida, H., Hosokawa, M., et al., Accelerated Accumulation of Somatic Mutations in the Senescence-Accelerated Mouse, Nat. Genet., 1998, vol. 19, no. 2, pp. 116–117.

    Article  PubMed  CAS  Google Scholar 

  7. Uryvaeva, I.V., Marshak, T.L., Zakhidov, S.T., et al., Age-Related Accumulation of Micronuclear Aberration in the Liver Cells of the Senescence Accelerated Mice (SAM), Dokl. Akad. Nauk, 1999, vol. 368, pp. 703–705.

    PubMed  CAS  Google Scholar 

  8. Guo, Z., Toichi, E., Hosono, M., et al., Genetic Analysis of Lifespan in Hybrid Progeny Derived from the SAMP1 Mouse Strain with Accelerated Senescence, Mech. Aging Dev., 2000, vol. 118, pp. 35–44.

    Article  PubMed  CAS  Google Scholar 

  9. Hayashi, M., Nishida, K., Endoh, D., and Okui, T., Production of Age-Related DNA Strand Breakage in Brain Cells of Senescence-Accelerated Prone (SAMP1) Mouse, Exp. Anim., 2003, vol. 52, no. 4, pp. 353–357.

    Article  PubMed  CAS  Google Scholar 

  10. Carp, R.I., Meeker, H.C., Kozlowski, P., and Sersen, E.A., An Endogenous Retrovirus and Exogenous Scrapie in a Mouse Model of Aging, Trends Microbiol., 2000, vol. 8, pp. 39–42.

    Article  PubMed  CAS  Google Scholar 

  11. Zakhidov, S.G., Gordeeva, O.F., and Marshak, T.L., Biological Model of Accelerated Senescence: 1. The Rate of the Spontaneous Mutation Process in Spermatogenesis of Senescence-Accelerated Mice (SAM), Izv. Akad. Nauk, Ser. Biol., 2001, no. 1, pp. 23–30.

  12. Zakhidov, S.T., Marshak, T.L., Uryvaeva, I.V., et al., Cytogenetic Aberrations in the Cells of Liver and Spermatogenic Epithelium in Senescence Accelerated SAMP1 and SAMR1 Mice, Ontogenez, 2002, vol. 33, no. 6, pp. 444–456.

    PubMed  CAS  Google Scholar 

  13. Gopko, A.V., Zakhidov, S.T., Marshak, T.L., et al., Genetic Instability of Male Gametes in Long-Lived Mice of the SAMP1 Strain Prone to Accelerated Senescence, Dokl. Akad. Nauk, 2003, vol. 392, no. 2, pp. 267–270.

    Google Scholar 

  14. Wyrobek, A. and Bruce, W., Chemical Induction of Sperm Abnormalities in Mice, Chemical Mutagen, vol. 5, Hollaender, A. and de Serres, F.J., Eds., New York: Plenum, 1978, pp. 257–286.

    Google Scholar 

  15. Lähdetie, J., Micronuclei Induced during Meiosis by Ethyl Methanesulfonate, Cyclophosphamide and Dimethylbenzanthracene in Male Rats, Mutat. Res., 1983, vol. 120, no. 4, pp. 257–260.

    Article  PubMed  Google Scholar 

  16. Tates, A.D., Dietrich, A.J., de Vogel, N., et al., A Micronucleus Method for Detection of Meiotic Micronuclei in Male Germ Cells of Mammals, Mutat. Res., 1983, vol. 121, no. 2, pp. 131–138.

    Article  PubMed  CAS  Google Scholar 

  17. Allen, J.W., Collins, B.W., and Evansky, P.A., Spermatid Micronucleus Analyses of Trichloro-Ethylene and Chloral Hydrate Effects in Mice, Mutat. Res., 1994, vol. 323, pp. 81–88.

    Article  PubMed  CAS  Google Scholar 

  18. Zakhidov, S.T., Paranyushkina, L.P., Khoda Kh.A., et al., The Influence of Chemical Mutagens on Mammal Spermatogenesis: Cytogenetic Analysis, Izv. Akad. Nauk, Ser. Biol., 1994, no. 3, pp. 353–362.

  19. Zakhidov, S.T. and Gordeeva, O.F., Features of Development of Male Sex Cells in Mice Subjected to the Mutagens Dipine and Nitrosomethylurea (NMM) during the Prenatal Period, Dokl. Akad. Nauk, 1998, vol. 362, no. 1, pp. 127–129.

    PubMed  CAS  Google Scholar 

  20. Kunugita, N., Kakihara, H., Kawamoto, T., and Norimura, T., Micronuclei Induced by Low Dose Rate Irradiation in Early Spermatids of p53 Null and Wild Mice, J. Radiat. Res. (Tokyo), 2002, vol. 43, pp. 205–207.

    Article  Google Scholar 

  21. Müller, W.-U. and Streffer, C., Micronucleus Assays, Advances in Mutogenetic Research, Obe, G., Ed., London, 1994, vol. 5, pp. 3–135.

  22. Rapoport, I.A., Mikrogenetika, (Microgenetics), Moscow: Nauka, 1965.

    Google Scholar 

  23. Parnes, V.A., Rapoport, I.A., and Levina, D.M., Genetic Analysis of the Effect of Rous Sarcoma Virus (Schmidt-Ruppin Strain) on Drosophila, Dokl. Akad. Nauk SSSR, 1968, vol. 182, pp. 953–956.

    PubMed  CAS  Google Scholar 

  24. Jin, D.Y., Spencer, F., and Jeang, K.T., Human T Cell Leukemia Virus Type 1 Oncoprotein Tax Targets the Human Mitotic Checkpoint Protein MAD1, Cell, 1998, vol. 93, no. 1, pp. 81–91.

    Article  PubMed  CAS  Google Scholar 

  25. Shimura, M., Tanaka, Y., Nakamura, S., et al., Micronuclei Formation and Aneuploidy Induced by Vpr, an Accessory Gene of Human Immunodeficiency Virus Type 1, FASEB J., 1999, vol. 13, no. 6, pp. 621–637.

    PubMed  CAS  Google Scholar 

  26. Takehashi, M., Kanatsu-Shinochara, M., Inoue, K., et al., Adenovirus-Mediated Gene Delivery into Mouse Spermatogonial Stem Cells, Proc. Natl. Acad. Sci. USA, 2007, vol. 104, pp. 2596–2601.

    Article  PubMed  CAS  Google Scholar 

  27. Hosokawa, M., Fuisawa, H., Ax, S., et al., Age-Associated DNA Damage Is Accelerated in the Senescence-Accelerated Mice, Mech. Aging Dev., 2000, vol. 118, pp. 61–70.

    Article  PubMed  CAS  Google Scholar 

  28. Boldyrev, A.A., Yuneva, M.O., Sorokina, G.G., et al., Antioxidant Systems in Tissues of Senescence Accelerated Mice (SAM) of SAMPI Line, Characterized by Accelerated Accumulation of Senile Features, Biokhimiya, 2001, vol. 66, no. 10, pp. 1430–1437.

    Google Scholar 

  29. Rapoport, I.A., Enzyme Control of Cell Mutagenesis, in Khimicheskii mutagenez i selektsiya (Chemical Mutagenesis and Breeding), Moscow: Nauka, 1971, pp. 113–129.

    Google Scholar 

  30. De Rooij, D.G., Stem Cells in the Testis, Int. J. Exp. Pathol., 1998, vol. 79, no. 2, pp. 67–80.

    Article  PubMed  Google Scholar 

  31. Meistrich, M.L., Critical Components of Testicular Function and Sensitivity to Disruption, Biol. Reprod., 1986, vol. 34, pp. 17–28.

    Article  PubMed  CAS  Google Scholar 

  32. Kallio, M. and Lähdetie, J., Early G1 in the Male Rat Meiotic Cell Cycle Is Hypersensitive to N-Methyl-N-Nitrosourea-Induced Micronucleus Formation, Mutagenesis, 1995, vol. 10, pp. 279–285.

    Article  PubMed  CAS  Google Scholar 

  33. Russell, L.B., Hansicker, P.R., and Russell, W.L., Comparison of the Genetic Equimolar Doses of ENU and MNU: While the Chemicals Differ Dramatically in Their Mutagenicity in Stem-Cell Spermatogonia, Both Elicit Very High Mutation Rates in Differentiating Spermatogonia, Mutat. Res., 2007, vol. 606, pp. 181–195.

    Google Scholar 

  34. Rapoport, I.A., Chromosomes in the Repair Process, in Khimicheskii mutagenez i immunitet (Chemical Mutagenesis and Immunity), Moscow: Nauka, 1980, pp. 3–35.

    Google Scholar 

  35. Meistrich, M.L., Goldstein, L.S., and Wyrobeck, A.J., Long-Term Infertility and Dominant Lethal Mutations in Male Mice Treated with Adriamycin, Mutat. Res., 1985, vol. 152, pp. 53–65.

    PubMed  CAS  Google Scholar 

  36. Rapoport, I.A., 75% of Sex-Linked Mutations under the Influence of Diethylsulfate as a Criterion of Nonroentgen-Mimetic Mechanism, Byul. Mosk. O-va. Ispytatelei Prirody, Otdelenie Biol., 1963, no. 5, pp. 103–108.

Download references

Author information

Authors and Affiliations

  1. Department of Embryology, Moscow State University, Moscow, 119992, Russia

    S. T. Zakhidov, E. A. Malolina & I. A. Zelenina

  2. Kol’tsov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, 119334, Russia

    S. T. Zakhidov, A. Yu. Kulibin & T. L. Marshak

Authors
  1. S. T. Zakhidov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Yu. Kulibin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. L. Marshak
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. A. Malolina
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I. A. Zelenina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. T. Zakhidov.

Additional information

Original Russian Text © S.T. Zakhidov, A.Yu. Kulibin, T.L. Marshak, E.A. Malolina, I.A. Zelenina, 2008, published in Genetika, 2008, Vol. 44, No. 11, pp. 1539–1546.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zakhidov, S.T., Kulibin, A.Y., Marshak, T.L. et al. Estimation of the frequencies of induced mutations in spermatogenic cells of senescence-accelerated prone mice of the SAMP1 strain. Russ J Genet 44, 1338–1344 (2008). https://doi.org/10.1134/S1022795408110136

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1022795408110136

Keywords

Search

Navigation