Inhibition of Dimethylnitrosamine-Induced Strand Breaks in Liver DNA and Liver Cell Necrosis by Diethyldithiocarbamate 2
- 1 February 1977
- journal article
- research article
- Published by Oxford University Press (OUP) in JNCI Journal of the National Cancer Institute
- Vol. 58 (2), 263-271
- https://doi.org/10.1093/jnci/58.2.263
Abstract
Diethyldithiocarbamate (DEDTC) prevented dimethylnitrosamine (DMN)-induced strand breaks in liver DNA and liver cell necrosis in male Wistar rats. In contrast, DEDTC did not inhibit the fragmentation of liver DNA caused by several other chemical carcinogens (N-hydroxy-2-acetylaminofluorene, 3-hydroxyxanthine, aflatoxin B1N-acetoxy-2-acetylaminofluorene, methyl methanesulfonate, methylnitrosourea, and methylazoxymethanol acetate), whether or not they required metabolic activation. Aminoacetonitrile exerted an action similar to that of DEDTC. The inhibitory effect was transitory, lasting at least for 4 hours, and protection for longer than 4 hours required multiple administrations of DEDTC. DEDTC also inhibited the serum clearance of DMN, methylation of liver DNA, and oxidative demethylation of DMN in the in vitro hepatic microsomal system prepared from either male Wistar rats or from hamsters. Interference of the metabolism of DMN appeared to be the mechanism by which DEDTC arrested DMN-induced biochemical and biologic effects.Keywords
This publication has 10 references indexed in Scilit:
- Determination of dimethylnitrosamine and nitrosoproline by differential pulse polarographyAnalytical Chemistry, 1975
- Isolation of deoxyribonucleic acid from mammalian tissuesBiochemical Journal, 1967
- Variations in ultrastructural nuclear changes in hepatocarcinogenesisBiochemical Pharmacology, 1967
- Density-Gradient centrifugation of DNA in a fixed-angle rotorBiochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1966
- A nuclease specific for heat-denatured DNA isolated from a product of Aspergillus oryzaeBiochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis, 1966
- Metabolism of disulfiram and diethyldithiocarbamate in rats with demonstration of an in vivo ethanol-induced inhibition of the glucuronic acid conjugation of the thiolBiochemical Pharmacology, 1965
- PREFERENTIAL STAINING OF NUCLEIC ACID-CONTAINING STRUCTURES FOR ELECTRON MICROSCOPYThe Journal of cell biology, 1961
- Toxic liver injury. The metabolism of dimethylnitrosamineBiochemical Journal, 1956
- A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acidBiochemical Journal, 1956
- The colorimetric estimation of formaldehyde by means of the Hantzsch reactionBiochemical Journal, 1953