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Mechanistic Studies of Acetamide Hepatocarcinogenicity

  • Erik Dybing
  • W. Perry Gordon
  • Erik J. Søderlund
  • Jørn A. Holme
  • Edgar Rivedal
  • Snorri S. Thorgeirsson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)

Abstract

Feeding male Leeds rats a diet containing 5 % acetamide (AA) for 17 months resulted in the development of hepatic cell neoplasms in all animals (Flaks et al., 1983). Many studies have reported that AA does not show genotoxic effects. However, Pienta et al. (1977) found that AA transformed Syrian hamster embryo cells in culture. N-Hydroxyacetamide (N-OH-AA), a possible metabolite of AA, has been approved by the US Food and Drug Administration under the orphan drug products program for treatment of infection-induced renal stones (in: Putcha et al., 1984). This study was undertaken attempting to shed light on the mechanism of AA hepatocarcinogenicity.

Keywords

Covalent Binding Diethyl Maleate Alkylating Activity Alkaline Elution Syrian Hamster Embryo Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Ames, B.N., McCann, J., and Yamasaki, E., 1975, Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test, Mutation Res., 31: 347.Google Scholar
  2. Anundi, I., Högberg, J., and Stead, A.H., 1979, Glutathione depletion in isolated hepatocytes: its relation,to lipid peroxidation and cell damage, Acta Pharmacol. Toxicol., 45: 45.CrossRefGoogle Scholar
  3. Fishbein, W.N., Daly, J., and Streeter, C.L., 1969, Preparation and some properties of stable and carbon-14 and tritium labelled short-chain aliphatic hydroxamic acids, Anal. Biochem., 28: 13.PubMedCrossRefGoogle Scholar
  4. Flaks, B., Trevan, M.T., and A. Flaks, 1983, An electron microscope study of hepatocellular changes in the rat during chronic treatment with acetamide. Parenchyma, foci and neoplasms, Carcinogenesis, 4: 1117.PubMedCrossRefGoogle Scholar
  5. Holme, J.A. and Soderlund, E.J., 1984, Unscheduled DNA synthesis of rat hepatocytes in monolayer culture, Muta tion Res., 126: 205.CrossRefGoogle Scholar
  6. Jackson, B. and Desau, F.I., 1961, Liver tumors in rats fed acetamide, Lab. Invest., 10: 909.PubMedGoogle Scholar
  7. Kohn, K.W., Erickson, L.C., Ewig, R.A.G., and Qwelling, L.A., 1981, Measurement of strand breaks and cross-links by alkaline elution, in: “DNA Repair: A Laboratory Manual of Recent Procedures”, E.C. Friedberg and P.C. Hanawalt, eds., Marcel Dekker, New York.Google Scholar
  8. Pienta, R.J., Poiley, J.A., and Lebherz, W.B., 1977, Morphological transformation of early passage of golden Syrian hamster embryo cells dervied from cryopreserved primary cultures as a reliable in vitro bioassay for identifying diverse carcinogens, Int. J. Cancer, 19: 642.PubMedCrossRefGoogle Scholar
  9. Putcha, L., Gr}4fith, D.P., and Feldman, S.i41984, Disposition of C-acetohydroxamic acid and C-acetamide in the rat, Drug Metab. Disp., 12: 438.Google Scholar
  10. Søderlund, E.J., Nelson, S.D., von Bahr, C., and Dybing, E., 1982, Species differences in kidney toxicity and metabolic activation of tris(2,3-dibromopropyl)phosphate, Fund. Appl. Toxicol, 2: 187.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Erik Dybing
    • 1
  • W. Perry Gordon
    • 2
  • Erik J. Søderlund
    • 1
  • Jørn A. Holme
    • 1
  • Edgar Rivedal
    • 3
  • Snorri S. Thorgeirsson
    • 4
  1. 1.National Institute of Public HealthOsloNorway
  2. 2.University of WashingtonSeattleUSA
  3. 3.The Norwegian Radium HospitalOsloNorway
  4. 4.National Cancer InstituteBethesdaUSA

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