Influence of dithiocarbamates on the metabolism and toxicity of N-nitrosodimethylamine in rats. 1990

N Frank, and B Bertram, and H R Scherf, and M Wiessler
Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.

Five secondary amines and secondary amino acids were reacted with carbon disulfide to yield dithiocarbamates. These compounds were tested for their influence on biochemical parameters and on some biological effects of N-nitrosodimethylamine (NDMA). The following results were found. (i) All dithiocarbamates tested reduced the activity of N-nitrosodiethylamine-deethylase and completely inhibited the N-nitrosodimethylamine-demethylase in the rat liver. A striking influence on the glutathione content and on the activity of glutathione-S-transferase and glutathione-reductase was not observed. (ii) The excretion of unmetabolized N-nitrosodimethylamine in rat urine during 24 h increased from 0.1% without pretreatment to 3.6% of the given dose on combination with a single dose of dithiocarbamate. (iii) The acute toxicity of NDMA could be reduced with diethanol-dithiocarbamate. After a single simultaneous application of the inhibitor with NDMA, the LD50 was increased from 40 to 66 mg/kg. When the sulfur compound was administered twice, both simultaneously and 24 h after the nitrosamine, lethality was almost completely inhibited. We conclude from these results that dithiocarbamates may be suitable compounds for chemoprevention of nitrosamine-induced tumors.

UI MeSH Term Description Entries
D008297 Male Males
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D003640 Dealkylation The removing of alkyl groups from a compound. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Dealkylations
D004128 Dimethylnitrosamine A nitrosamine derivative with alkylating, carcinogenic, and mutagenic properties. It causes serious liver damage and is a hepatocarcinogen in rodents. Nitrosodimethylamine,N-Nitrosodimethylamine,NDMA Nitrosodimethylamine,N Nitrosodimethylamine,Nitrosodimethylamine, NDMA
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D005979 Glutathione Peroxidase An enzyme catalyzing the oxidation of 2 moles of GLUTATHIONE in the presence of HYDROGEN PEROXIDE to yield oxidized glutathione and water. Cytosolic Glutathione Peroxidase,Glutathione Lipoperoxidase,Selenoglutathione Peroxidase,Glutathione Peroxidase, Cytosolic,Lipoperoxidase, Glutathione,Peroxidase, Glutathione,Peroxidase, Selenoglutathione
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013859 Thiocarbamates Carbamates in which the -CO- group has been replaced by a -CS- group. Thiocarbamate
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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