Inhibition by cysteamine of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats.
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.
Tatsuta
M
M
Department of Gastrointestinal Oncology, Center for Adult Diseases, Osaka, Japan.
Iishi
H
H
Baba
M
M
D000818:Animals; D003543:Cysteamine / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D005954:Glucosephosphate Dehydrogenase / Q000032:analysis; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D009602:Nitrosamines; D009638:Norepinephrine / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000032:analysis
D009602:Nitrosamines; C002741:N-nitrosomorpholine; D003543:Cysteamine; D004247:DNA; D005954:Glucosephosphate Dehydrogenase; D005723:gamma-Glutamyltransferase; D009638:Norepinephrine