Skip to main content
Log in

Mutagenicity test systems for the detection of chromosome aberrations in vivo

  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

In mutagenicity testing of pharmaceuticals it is advisable, whenever possible, to use in vivo mammalian systems where the pharmacokinetic properties of a drug would be more or less similar to those in man. However, although there are a number of different genetic endpoints which are important in mutagen testing, sufficiently validated, practical and well documented in vivo test systems exist only for stuctural chromosome aberrations.

This paper provides an overview of existing in vivo test systems for the detection of chromosome aberrations. Emphasis has been laid on the functions, advantages and limitations of the three tests recommended in the guidelines of the European Community; first, the metaphase analysis assay, and, as alternatives, the micronucleus test and the dominant lethal test.

These three test are then also discussed from the viewpoint of our own practical experience.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Allen JW, Skuller CF, Mendes RW, Latt SA (1977) A simplified technique for in vivo analysis of sister chromatid exchanges using 5-bromodeoxy ridine tablets. Cytogenet Cell Genet 18:231–237

    Google Scholar 

  • Bateman AJ (1977) The dominant lethal assay in the male mouse. In: Kilbey B, Legator M, Nichols W, Ramel C (eds) Handbook of mutagenicity test procedures. Elsevier, Amsterdam New York Oxford, p 243

    Google Scholar 

  • Bateman AJ, Epstein SS (1971) Dominant lethal mutations in mammals. In: Hollaender A (ed) Chemical mutagens, vol 2. Plenum Press, New York London, p 541

    Google Scholar 

  • Binkert F, Schmid W (1977) Pre-implantation embryos of Chinese hamster. Mutat Res 46:62–86

    Google Scholar 

  • Brewen JG, Preston RJ (1978) Analysis of chromosome aberrations in mammalian germ cells. In: Hollaender A (ed) Chemical mutagens, vol 5. Plenum Press, New York London, p 127

    Google Scholar 

  • Cohen MM, Hirschhorn K (1971) Cytogenetic studies in animals. In: Hollaender A (ed) Chemical mutagens, vol 2. Plenum Press, New York London, p 515

    Google Scholar 

  • EEMS-Report (1978) Mutagenicity Screening: General principles and minimal criteria. Mutat Res 53:361–370

    Google Scholar 

  • Evans HJ (1976) Cytological methods for detecting chemical mutagens. In: Hollaender A (ed) Chemical mutagens, vol 4. Plenum Press, New York London, p 1

    Google Scholar 

  • Evans HJ, D'Riordan ML (1977) Human peripheral blood lymphocytes for the analysis of chromosome aberrations in mutagen tests. In: Kilbey BJ, Legator M, Nichols W, Ramel C (eds) Handbook of mutagenicity test procedures. Elsevier, Amsterdam New York Oxford, p 261

    Google Scholar 

  • Generoso WM, Cain KT, Huff SW, Gosslee DG (1978) Heritable translocation test in mice. In: Hollaender A (ed) Chemical mutagens, vol 5. Plenum Press, New York London, p 55

    Google Scholar 

  • Kilian DJ, Moreland FM, Benge MC, Legator MS, Whorton EB (1977) A collaborative study to measure interlaboratory variation with the in vivo bone marrow metaphase procedure. In: Kilbey BJ, Legator M, Nichols W, Ramel C (eds) Handbook of mutagenicity test procedure. Elsevier, Amsterdam New York Oxford, p 243

    Google Scholar 

  • Latt SA, Allen JW, Rogers WE, Juergens LA (1977) In vitro and in vivo analysis of sister chromatid exchange formation. In: Kilbey BJ, Legator M, Nichols W, Ramel C (eds) Handbook of mutagenicity test procedures. Elsevier, Amsterdam New York Oxford, p 275

    Google Scholar 

  • Léonard A (1973) Observations on meiotic chromosomes of the male mouse as a test of the potential mutagenicity of chemicals in mammals. In: Hollaender A (ed) Chemical mutagens, vol 3. Plenum Press, New York London, p 21

    Google Scholar 

  • Matter BE (1976a) Problems of testing drugs for potential mutagenicity. Mutat Res 38:243–258

    Google Scholar 

  • Matter BE (1980) Mutagenicity screening of new drugs. In: Alacevic M (ed) Progress in Environmental Mutagenesis. Elsevier/North-Holland, Amsterdam, p 191

    Google Scholar 

  • Matter BE, Grauwiler J (1974) Micronuclei in bone marrow cells. Mutat Res 23:239–249

    Google Scholar 

  • Matter BE, Jaeger I (1976) Premature chromosome condensation, structural chromosome aberrations, and micronuclei in early mouse embryos. Mutat Res 33:251–260

    Google Scholar 

  • Matter BE, Tsuchimoto T, Deyssenroth H (1978) Failure to detect dominant lethal mutations and effects on reproductive capacity in mice exposed to dihydro-ergotoxine mesylate. Drug Res 28:2286–2290

    Google Scholar 

  • Notes for Guidance on the Testing of Medicinal Products for Their Mutagenic Potential (1979) Draft Guidelines, European Community, Brussels

  • Röhrborn G, Hausmann I, Buckel U (1977) Cytogenetic analysis of pre- and postovulatory ocytes and pre-implantation embryos in mutagenesis of mammals. In: Kilbey BJ, Legator M, Nichols W, Ramel C (eds) Handbook of mutagenicity test procedures. Elsevier, Amsterdam New York Oxford, p 301

    Google Scholar 

  • Russel LB (1976) Numerical sex-chromosome anomalies in mammals. Their spontaneous occurrence and use in mutagenesis studies. In: Hollaender A (ed) Chemical mutagens, vol 4. Plenum Press, New York London, p 55

    Google Scholar 

  • Schmid W (1976) The micronucleus test for cytogenetic analysis. In: Hollaender A (ed) Chemical mutagens, vol 4. Plenum Press, New York London, p 31

    Google Scholar 

  • Schmid W (1977) The micronucleus test. In: Kilbey BJ, Legator M, Nichols W, Ramel C (eds) Handbook of mutagenicity test procedures. Elsevier, Amsterdam New York Oxford, p 235

    Google Scholar 

  • Staub JE, Matter BE (1976) Heritable reciprocal translocations and sperm abnormalities in the F1-offspring of male mice treated with TEM. Arch Genet 49/50:29–41

    Google Scholar 

  • Tsuchimoto T, Stalder GR (1976) Effects of an ergot derivative on human lymphocyte chromosomes in vivo. Drug Res 26:2101–2103

    Google Scholar 

  • Tsuchimoto T, Matter BE (1979) In vivo cytogenetic screening methods for mutagens, with special reference to the micronucleus test. Arch Toxicol 42:239–248

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Chemical Substances Mentioned: Trisethylenemelamine (TEM), Trenimon, Cyclophosphamide, Mitomycin C, Colchicine, Benzimidazol carbamate, Azathioprine

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matter, B.E., Tsuchimoto, T. Mutagenicity test systems for the detection of chromosome aberrations in vivo. Arch. Toxicol. 46, 89–98 (1980). https://doi.org/10.1007/BF00361248

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00361248

Key words

Navigation