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. 1992 Jun;118(6):401–404. doi: 10.1007/BF01629420

Proline dithiocarbamate inhibitsN-nitrosodiethylamine induced liver carcinogenesis

Dimiter Hadjiolov 1, Norbert Frank 2,✉, Christiane Moog 2, Konstantin Spirov 1
PMCID: PMC12201744  PMID: 1377694

Abstract

A study was conducted to determine the toxicity of different dithiocarbamates and of disulfiram. In an experiment showing the cytotoxicity against murine spleen lymphocytes, proline dithiocarbamate (PDTC) and thioproline dithiocarbamate showed the lowest toxicity. Therefore one of them was selected and different doses of the hydrophilic PDTC were checked for their ability to affect the development of liver and oesophagus tumours induced in BD-6 rats byN-nitrosodiethylamine (NDEA). Rats were injected i.p. with 80 mg/kg NDEA once weekly for 10 weeks. Administration of PDTC, 1 h before and 24 h after the carcinogen, markedly decreased the number of rats developing NDEA-induced hepatocellular carcinoma and liver haemangioendothelioma. A 59%–77% reduction in the incidence of liver tumours was found in the different groups when the carcinogen was administered in combination with the inhibitor. For least 40 weeks after the start of the experiment PDTC protected the liver from NDEA carcinogenesis and did not shift the tumour development to any other organ. PDTC did not significantly affect the weight gain of the experimental animals. We conclude that parenteral administration of PDTC seems to represent a promising approach in chemoprevention of liver carcinogenesis.

Key words: Proline dithiocarbamate, Liver carcinogenesis, Disulfiram, Dithiocarbamates

Abbreviations

NDEA

N-nitrosodiethylamine

PDTC

proline dithiocarbamate

SDTC

sarcosine dithiocarbamate

TDTC

throproline dithiocarbamate

DDTC

diethyldithiocarbamate

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