Original Articles
Copyright ©The Author(s) 1998. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 15, 1998; 4(2): 128-132
Published online Apr 15, 1998. doi: 10.3748/wjg.v4.i2.128
Endotoxins enhance hepatocarcinogenesis induced by oral intake of thioacetamide in rats
Jin-Ming Yang, De-Wu Han, Chun-Ming Xie, Quan-Cheng Liang, Yuan-Chang Zhao, Xue-Hui Ma
Jin-Ming Yang, Yuan-Chang Zhao, Xue-Hui Ma, Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China
Quan-Cheng Liang, Shanxi Second People’s Hospital, Taiyuan 030012, Shanxi Province, China
Jin-Ming Yang, associate professor and Ph.D. candidate in pathophysiology, majoring hepatic pathophysiology, having 12 papers published. Presented at the International Symposium on Hepatology, August 12-16, 1997, Beijing, China.
Author contributions: All authors contributed equally to the work.
Correspondence to: Professor De-Wu Han, Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, Shanxi Province, China.
Telephone: +86·351·4135067 Fax: +86·351·2024239
Received: September 1, 1997
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.

Keywords: liver neoplasms, carcinoma, hepatocellular, endotoxins, thioacetamide, glutamyl transpeptidase/metabolism, flow cytometry, DNA, neoplasm, rats, Wistar