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Effects of disulfiram on the metabolism of nitrosodiethylamine during liver carcinogenesis

  • Original Papers
  • Experimental Oncology
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Summary

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.

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Abbreviations

DSF:

disulfiram

NDEA:

N-nitrosodiethylamine

References

  • 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

    PubMed  Google Scholar 

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

    Google Scholar 

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

  • 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

    PubMed  Google Scholar 

  • 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

    Article  PubMed  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

  • 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

    PubMed  Google Scholar 

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

    Google Scholar 

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

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • 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

    Article  Google Scholar 

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

    Google Scholar 

  • 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

    PubMed  Google Scholar 

  • 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

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

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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

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  • DOI: https://doi.org/10.1007/BF00390458

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