INHIBITION BY SOMATOSTATIN OF HEPATOCARCINOGENESIS INDUCED BY N-NITROSOMORPHOLINE IN SPRAGUE-DAWLEY RATS

The effect of somatostatin on hepatocarcinogenesis induced by N-nitros omorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats w ere given drinking water containing NNM for 8 weeks and s.c. injection s of 200 mu g/kg body wt of somatostatin every other day from the begi nning of the experiment until the end of week 16. Pre-neoplastic and n eoplastic lesions staining for gamma-glutamyl transpeptidase (GGT) or placental type glutathione-S-transferase (GST-P) were examined histoch emically. Administration of somatostatin for 16 weeks resulted in sign ificant reduction in the percentage volume of GGT-positive and GST-P-p ositive lesions. The incidence, number and size of hepatocellular carc inomas were significantly less in rats treated with somatostatin than in untreated rate. Administration of somatostatin significantly decrea sed the labeling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that somatostatin inhibits hepatocarcinogenes is and that this effect may be related to its effect in decreasing cel l proliferation in pre-neoplastic lesions.