Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Effects of disulfiram on the metabolism of nitrosodiethylamine during liver carcinogenesis

  • 22 Accesses

  • 12 Citations


We have studied the effects of disulfiram (DSF) administration on the metabolism of nitrosodiethylamine (NDEA) in rats during acute and chronic administration. DSF was found to have the following effects during the course of carcinogenesis: (a) marked decrease in the exhalation of 14CO2 derived from 14C-NDEA; (b) reduction of the total levels of DNA and RNA ethylation in the liver. In acute experiments DSF caused an incrase in the amount of NDEA in organs and in the urine. We suggest that inhibition of NDEA biotransformation and the subsequent decrease in the total level of DNA ethylation may prevent specific chemical interactions relevant to carcinogenesis.

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







  1. Abanobi SE, Popp JA, Chang SK, Harrington GW, Lotlikar FD, Hadjiolov D, Levitt M, Rajalakshmi S, Sarma DSR (1977) Inhibition of dimethylnitrosamine-induced strand breaks in liver DNA and liver cell necrosis by diethyldithiocarbamate. J Natl Cancer Inst 58:263–271

  2. Balsiger RW, Montgomery JA (1960) Synthesis of potential anticancer agents. XXV. Preparation of 6-alkoxy-2-aminopurines, J Org Chem 25:1573–1575

  3. Brookes P, Lawley PD (1961) The alkylation of guanosine and guanilic acid. J Chem Soc 3923

  4. Frank N, Hadjiolov D, Bertram B, Wiessler M (1980) Effect of disulfiram on the alkylation of liver DNA by nitrosodiethylamine. J Cancer Res Clin Oncol 97:209–212

  5. Frei JV, Lawley PD (1975) Methylation of DNA in various organs of C57B1 mice by a carcinogenic dose of N-Methyl-N-nitrosourea and stability of some methylation products up to 18 hours. Chem Biol Interact 10:413–427

  6. Hadjiolov D (1971) The inhibition of dimethylnitrosamine carcinogenesis in rat liver by aminoacetonitrile. Z Krebsforsch 76:91–92

  7. Hadjiolov D, Frank N, Schmähl D (1977) Inhibition of diethylnitrosamine-induced strand breaks in liver DNA by disulfiram. Z Krebsforsch 90:107–109

  8. Irving CC, Tice AJ, Murphy WM (1979) Inhibition of N-n-butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary bladder cancer in rats by administration of disulfiram in the diet. Cancer Res 39:3040–3043

  9. Kidson C, Ralph R, Kirby K (1963) Isolation characteristics of rapidly labelled RNA from normal rat liver. J Mol Biol 7:312–315

  10. Kleihues P, Margison GP (1976) Exhaustion and recovery of repair excision of 0-6-methylguanine from rat liver DNA. Nature 259:153–155

  11. Mundt D, Hadjiolov D (1974) Effect of aminoacetonitrile on the metabolism of diethylnitrosamine during liver carcinogenesis. J Natl Cancer Inst 52:1515–1520

  12. Pegg AE (1977) Alkylation of rat liver DNA by dimethylnitrosamine: Effect of dosage on O6-methylguanine levels. J Natl Cancer Inst. 58:681–687

  13. Schmähl D, Krüger FW, Habs M, Diehl B (1976) Influence of disulfiram on the organotropy of the carcinogenic effect of dimethylnitrosamine and diethylnitrosamine in rats. Z Krebsforsch 85:271–276

  14. Spiegelhalder B, Eisenbrand G, Preussmann R (1983) In: Environmental carcinogenesis — Selected methods of analysis: Volatile nitrosamines. IARC, Lyons (Scientific publication no. 45)

  15. Swann PF, Magee PN (1968) Nitrosamine-induced carcinogenesis. The alkylation of nucleic acids of the rat by N-methyl-N-nitrosourea, dimethylnitrosamine, dimethylsulphate and methylmethanesulphonate. Biochem J 110:39–47

  16. Uziel M, Koh CK, Cohn WE (1968) Rapid ionexchange chromatographic microanalysis of ultraviolet absorbing material and its application to nucleosides. Anal Biochem 25:77–98

  17. Wattenberg LW (1975) Inhibition of dimethylhydrazine-induced neoplasia of the large intestine by disulfiram. J Natl Cancer Inst 54:1005–1006

Download references

Author information

Correspondence to N. Frank.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hadjiolov, D., Frank, N., Mundt, D. et al. Effects of disulfiram on the metabolism of nitrosodiethylamine during liver carcinogenesis. J Cancer Res Clin Oncol 108, 281–285 (1984). https://doi.org/10.1007/BF00390458

Download citation

Key words

  • Disulfiram
  • Nitrosodiethylamine
  • Carcinogenesis
  • DNA
  • RNA
  • Alkylation
  • Metabolism