Abstract
The effect of cysteamine (2-aminoethanethiol hydrochloride) on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats received alternate-day s.c. injections of cysteamine, and beginning in experimental week 3 were given drinking water containing NNM for 8 weeks. Pre-neoplastic and neoplastic lesions staining positive for gamma-glutamyl transpeptidase (GGT) or glucose-6-phosphate dehydrogenase (G6PD) were examined by histochemical techniques. In week 18, quantitative histological analysis showed that prolonged administration of cysteamine resulted in a significant reduction in the number of GGT-positive and G6PD-positive hepatic lesions. Histologically, hepatocellular carcinomas were significantly fewer and smaller in GGT-positive and G6PD-positive lesions in rats treated with cysteamine than in untreated rats. Administration of cysteamine also caused a significant decrease in the liver norepinephrine concentration and in the labelling indices of pre-neoplastic lesions and the surrounding liver. Our findings indicate that cysteamine inhibits hepatocarcinogenesis; this may be related to its reducing effect on norepinephrine concentration in the liver and its subsequent inhibition of cell proliferation in neoplastic lesions and surrounding hepatocytes.
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