Skip to main content

Denitrosation of N-Nitrosodimethylamine in the Rat in Vivo

  • Chapter
  • 25 Accesses

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 283))

Abstract

The potent hepatocarcinogen N-nitrosodimethylamine (NDMA) has been shown to be metabolized by liver microsomes from acetone-induced rats via two pathways (Figure 1). While the denitrosation pathway has been studied fairly extensively in vitro (Keefer et al., 1987b; Wade et al., 1987; Amelizad et al., 1988), only a few tentative observations about its course in the intact animal have so far appeared in the literature (Heath and Dutton, 1958; Keefer et al., 1987a; Magee et al., 1988). The easiest and most direct assessment of denitrosation in vivo should come from measuring the extent of conversion of NDMA to MA, if the NDMA is labeled with carbon-14 so that the metabolically produced MA can be differentiated from the endogenous material that is known to be present (Davis and de Ropp, 1961).

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Amelizad, Z., Appel, K.E., Oesch, F., and Hildebrandt, A.G. (1988). Effect of antibodies against cytochrome P-450 on demethylation and denitrosation of Nnitrosodimethylamine and N-nitrosomethylaniline. J. Cancer Res. Clin. Oncol. 114, 380 - 384.

    Article  CAS  PubMed  Google Scholar 

  • Davis, E.J., and DeRopp, R.S. (1961). Metabolic origin of urinary methylamine in the rat. Nature (London) 190, 636 - 637.

    Article  CAS  Google Scholar 

  • Heath, D.F., and Dutton, A. (1958). The detection of metabolic products from dimethylnitrosamine in rats and mice. Biochem. J. 70, 619 - 626.

    CAS  PubMed  Google Scholar 

  • Heur, Y.-H., Streeter, A.J., Nims, R.W., and Keefer, L.K. (1989). The Fenton degradation as a nonenzymatic model for microsomal denitrosation of Nnitrosodimethylamine. Chem. Res. Toxicol. 2, 247 - 253.

    Article  CAS  PubMed  Google Scholar 

  • Houston, J.B. (1986). Drug metabolite kinetics. In Pharmacokinetics: Theory and Methodology (M. Rowland, and G. Tucker, Eds.), pp. 131-162, International Encyclopedia of Pharmacology and Therapeutics, Section 122, Pergamon Press, New York.

    Google Scholar 

  • Keefer, L.K., Lijinsky, W., and Garcia, H. (1973). Deuterium isotope effect on the carcinogenicity of dimethylnitrosamine in rat lover. J. Natl. Cancer Inst. 51, 299 - 302.

    CAS  PubMed  Google Scholar 

  • Keefer, L.K., Anjo, T., Heur, Y.-H., Yang, C.S., and Mico, b.A. (1987). Potential for metabolic deactivation of carcinogenic N-nitrosodimethylamine in vivo. In Relevance of N-Nitroso Compounds to Human Cancer: Exposure and Mechanisms (H. Bartsch, I.K. O’Neill, and R. Schulte-Hermann, Eds.), pp. 113-116, IARC Scientific Publications No. 84, International Agency for Research on Cancer, Lyon, France.

    Google Scholar 

  • Keefer, L.K., Anjo, T., Wade, D., Wang, T., and Yang, C.S. (1987). Concurrent generation of methylamine and nitrite during denitrosation of Nnitrosodimethylamine by rat liver microsomes. Cancer Res. 47, 447 - 452.

    CAS  PubMed  Google Scholar 

  • Magee, P.N., Harrington, G.W., Pylypiw, H., dollard, D., Kozeniauskas, R., Bevill, R.F., Thurmon, J., and Nelson, D. (1988). The metabolism of N- nitrosodimethylamine in the pig. Proc. Am. Assoc. Cancer Res. 29, 124.

    Google Scholar 

  • Streeter, a.J., Nims, R.W., Hrabie, J.A., Heur, Y.-H., and Keefer, L.K. (1989). Sex differences in the single-dose toxicokinetics of N-nitrosomethyl (2hydroxyethyl)amine in the rat. Cancer Res. 49, 1783 - 1789.

    CAS  PubMed  Google Scholar 

  • Swann, P.F., Mace, R., Angeles, R.M., and Keefer, L.K. (1983). Deuterium isotope effect on metabolism of N-nitrosodimethylamine in vivo in rat. Carcinogenesis (London) 4, 821 - 825.

    Article  CAS  Google Scholar 

  • Wade, D., Yang, C.S., Metral, C.J., roman, J.M., Hrabie, J.A., Riggs, C.W., Anjo, T., Keefer, L.K., and Mico, B.A. (1987). Deuterium isotope effect on denitrosation and demethylation of N-nitrosodimethylamine by rat liver microsomes. Cancer Res. 47, 3373 - 3377.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Plenum Press, New York

About this chapter

Cite this chapter

Streeter, A.J., Nims, R.W., Sheffels, P.R., Keefer, L.K. (1991). Denitrosation of N-Nitrosodimethylamine in the Rat in Vivo . In: Witmer, C.M., Snyder, R.R., Jollow, D.J., Kalf, G.F., Kocsis, J.J., Sipes, I.G. (eds) Biological Reactive Intermediates IV. Advances in Experimental Medicine and Biology, vol 283. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5877-0_49

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-5877-0_49

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5879-4

  • Online ISBN: 978-1-4684-5877-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics