Skip to main content
Log in

The influence of metabolism on mutagenic activity in the host-mediated assay

  • Published:
Archiv für Toxikologie Aims and scope Submit manuscript

Abstract

The problem to be examined is the extent to which induced changes in metabolism influence the mutagenic activity of several N-nitroso-compounds in the host-mediated assay. After pretreatment with carbon tetrachloride it is impossible to induce mutations with dimethylnitrosamine in the host-mediated assay system. Pretreatment with phenobarbital does not influence the mutagenic activity of this compound. Methyl-nitroso-nitroguanidine has mutagenic effects only when applied parenterally, but not when given orally. Methyl-nitrosourea induces mutations when injected subcutaneously and when given orally. These results may be explained by differences of absorption.

Zusammenfassung

Es wird untersucht, inwieweit induzierte Veränderungen des Metabolismus die mutagene Wirksamkeit einiger N-Nitrosoverbindungen im host-mediated assay beeinflussen können. Eine Vorbehandlung der Maus mit Tetrachlorkohlenstoff macht es unmöglich, mit Dimethylnitrosamin im host-mediated assay Mutationen auszulösen. Die Vorbehandlung mit Phenobarbital hat keinen Einfluß auf die mutagene Wirkung dieser Verbindung. Methyl-nitroso-nitroguanidin wirkt nur nach parenteraler, nicht nach oraler Applikation, mutagen. Methylnitrosoharnstoff induziert Mutationen bei subcutaner Injektion und oraler Gabe. Die Verschiedenheiten werden auf eine unterschiedliche Resorption zurückgeführt.

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

  • Cerdá-Olmedo, E., Hanawalt, P. C.: Diazomethane as the active agent in nitrosoguanidine mutagenesis and lethality. Molec. gen. Genet. 101, 191–202 (1968).

    Google Scholar 

  • Druckrey, H., Preussmann, R., Ivankovic, S., Schmähl, D.: Organotrope carcinogene Wirkungen bei 65 verschiedenen N-Nitroso-Verbindungen an BD-Ratten. Z. Krebsforsch. 69, 103–201 (1967).

    Google Scholar 

  • Ehling, U. H.: The multiple loci method. In: Chemical mutagenesis in mammals and man (F. Vogel and G. Röhrborn, eds.). Berlin-Heidelberg-New York: Springer 1970.

    Google Scholar 

  • Gabridge, M. G., Legator, M. S.: A host-mediated microbial assay for the detection of mutagenic compounds. Proc. Soc. exp. Biol. (N.Y.) 130, 831–834 (1969).

    Google Scholar 

  • —, Oswald, E. J., Legator, M. S.: The role of selection in the host-mediated assay for mutagenicity. Mutation Res. 7, 117–119 (1969).

    Google Scholar 

  • Heath, D. F.: The decomposition and toxicity of dialkylnitrosamines in rats. Biochem. J. 85, 72–91 (1962).

    Google Scholar 

  • Herken, H., Maibauer, D., Neubert, D.: Der Einfluß von Äthionin und anderen Lebergiften auf Fermentsysteme der Lebermikrosomen. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 233, 139–150 (1958).

    Google Scholar 

  • Legator, M. S.: The host-mediated assay, a practical procedure for evaluating potential mutagenic agents. In: Chemical mutagenesis in mammals and man (F. Vogel and G. Röhrborn, eds). Berlin-Heidelberg-New York: Springer 1970.

    Google Scholar 

  • Magee, P. N., Farber, E.: Toxic liver injury and carcinogenesis. Methylation of rat liver nucleic acids by dimethylnitrosamine in vivo. Biochem. J. 83, 114–124 (1962).

    Google Scholar 

  • —, Swann, P. F.: Nitroso compounds. Brit. med. Bull. 25, 240–244 (1969).

    Google Scholar 

  • Remmer, H.: Der beschleunigte Abbau von Pharmaka in den Lebermikrosomen unter dem Einfluß von Luminal. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 235, 279–290 (1959).

    Google Scholar 

  • Röhrborn, G.: The activity of alkylating agents. I. Sensitive mutable stages in spermatogenesis and oogenesis. In: Chemical mutagenesis in mammals and man (F. Vogel and G. Röhrborn, eds.). Berlin-Heidelberg-New York: Springer 1970.

    Google Scholar 

  • Schoental, R.: Carcinogenic activity of N-methyl-N-nitroso-N′-nitroguanidine. Nature (Lond.) 209, 726–727 (1966).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was sponsored by the Deutsche Forschungsgemeinschaft.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Propping, P., Buselmaier, W. The influence of metabolism on mutagenic activity in the host-mediated assay. Arch. Toxikol. 28, 129–134 (1971). https://doi.org/10.1007/BF00332388

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00332388

Key-Words

Schlüsselwörter

Navigation