Decreased expression of Bcl-x protein during hepatocarcinogenesis induced exogenously and endogenously in rats.

Abstract

Dysregulations of apoptosis have been widely recognized as important events in multi-stage carcinogenesis. Bcl-x, a member of the Bcl-2 family, is known to act as a regulator of apoptosis. The present study was conducted to assess the role of altered Bcl-x protein expression in exogenous and endogenous hepatocarcinogenesis in rats. In the short-term exogenous models, male Fischer 344 rats, 6 weeks old, were given a single intraperitoneal injection of diethylnitrosamine (DEN) at a dose of 200 mg / kg body weight, partially hepatectomized at the end of week 3, administered phenobarbital at a concentration of 0.05% from the end of week 2 for 6 weeks, and sacrificed. In the livers, glutathione S-transferase (GST-P)-positive, putative preneoplastic lesions were induced, and Bcl-x protein expression was decreased in 24.7% of such lesions. The incidence of GST-P-positive lesions with decreased Bcl-x increased depending on the size of the lesions; 18.9%, 32.4% and 86.5% in the lesions smaller than 0.03, between 0.03 and 0.3, and larger than 0.3 mm(2), respectively. In GST-P-positive lesions larger than 0.3 mm(2), both apoptosis induction and cell proliferation activity were enhanced when Bcl-x protein expression was decreased. In the long-term exogenous models, rats were given 10 mg / kg of DEN, partially hepatectomized 4 h after treatment, administered 0.5 mg / kg of colchicine at the end of days 1 and 3, subjected to a selection procedure, and sacrificed at the end of week 45. Hepatocellular carcinomas were induced with the decreased Bcl-x protein expression. In the endogenous model, rats were fed a choline-deficient, L-amino acid-defined diet for 16 or 80 weeks and sacrificed. Bcl-x protein expression was decreased both in GST-P-positive lesions and hepatocellular carcinoma. These results suggest that this decrease of Bcl-x protein might serve as an indicator of the advanced form of preneoplastic lesions, and that this decrease could also be associated with a potential to progress into carcinoma in both exogenous and endogenous hepatocarcinogenesis of rats.

• Authors: Y Hatanaka, D Nakae, M Mutai, K Hashizume, Y Kamihara, N Kinoshita, Y Tani, G Danno Gi, S Ohta, Y Konishi, H Ashida
• Journal: Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 92 Issue 12 Pg. 1270-7 (Dec 2001) ISSN: 0910-5050 [Print] Japan
• PMID: 11749691 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Alkylating Agents
• Bcl2l1 protein, rat
• Proto-Oncogene Proteins c-bcl-2
• bcl-X Protein
• Diethylnitrosamine
• Glutathione Transferase
• Choline

Topics

• Alkylating Agents (administration & dosage, pharmacology)
• Animals
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (chemically induced, genetics, metabolism, pathology)
• Cell Division (drug effects)
• Choline (metabolism)
• Diethylnitrosamine (administration & dosage, pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Glutathione Transferase (metabolism)
• In Situ Nick-End Labeling
• Male
• Precancerous Conditions (chemically induced, genetics, metabolism, pathology)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Rats
• Rats, Inbred F344
• bcl-X Protein