Published online Apr 15, 1998. doi: 10.3748/wjg.v4.i2.128
Revised: September 30, 1997
Accepted: October 15, 1997
Published online: April 15, 1998
AIM: To clarify whether endotoxin is of pathogenic importance for hepatocarcinogenesis,or the increased cancer risk results solely from thecirrhotic process.
METHODS: The rat model of hepatoma was treated by the intake of 0.03% thioacetamide in drinking water for six months. During induction of hepatoma, rats were additionally treated with splenectomy and/or lipopolysaccharide administration. The liver nuclear DNA index and proliferation index were quantitatively analyzed by flow cytometry. Hepatic histology was examined with light and electron microscopes. Plasmic endotoxin concentration and γ-glutamyl transpeptidase activity were measured, and hepatoma incidence was recorded.
RESULTS: Thioacetamide induced cirrhosis and hepatoma in Wistar rats with histology or regenerative nodule, fibrosis and neoplastic foci were quite similar to the pathogenic process of human cirrhosis leading to hepatoma. In comparison with TAA controls (DNA index: 1.15 ± 0.21), exo-endotoxin increased the DNA index by 7.8% (1.24 ± 0.25, P < 0.02) and hepatoma rate by 16.7. Splenectomy-induced enteric endotoxemia increased the DNA index by 25% (1.44 ± 0.15, P < 0.01) and hepatoma rate by 33%. A summation of the effects of these two factors increased the DNA index by 36% (P£¼0.01)and hepatoma incidence by 50%, moreover, the level of endotoxemia showed a close relation with DNA index (r = 0.96, P < 0.01), as well as with the occurrence rate of hepatoma (r = 0.00, P < 0.01). Histological findings further verified such alterations.
CONCLUSION: Lipopolysaccharide administration and/or splenectomy-induced enterogenic endotoxemia may enhance rat hepatocarcinogenesis induced by oral intake of thioacetamide.