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PMID: 9060843 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Hepatocellular neoplasms induced by low-number pancreatic islet transplants in streptozotocin diabetic rats.

The American journal of pathology ·Vol. 150 ·No. 3 ·1997-03-00 ·Pages 1071-87

Dombrowski F, Bannasch P, Pfeifer U

Abstract

We have previously demonstrated in short-term experiments that altered hepatocytes in liver acini draining the blood from intraportally transplanted pancreatic islets in streptozotocin-induced diabetic rats with mild persisting diabetes resemble those in preneoplastic foci of altered hepatocytes. We now present the results of long-term studies (up to 22 months) in this animal model. Glycogen-storing foci (which were the first parenchymal alteration observed some days after transplantation) persisted at least for 6 months, when the first mixed-cell foci and the first hepatocellular adenoma emerged. After 15 to 22 months, 86% of the animals exhibited at least one hepatocellular adenoma and four animals (19%) showed a hepatocellular carcinoma. The transplants were found in a close spatial relationship with the preneoplastic foci and the hepatocellular neoplasms. The mitotic indices, the 5-bromo-2'-desoxyuridine labeling indices and the apoptotic indices showed significant differences between the unaltered liver parenchyma, different types of preneoplastic foci, and hepatocellular neoplasms. The immunohistochemical expression of transforming growth factor-alpha increased during the stepwise development from glycogen-storing liver acini to hepatocellular carcinomas. Hepatocarcinogenesis in this new animal model is probably due to the hormonal and growth-stimulating effects of insulin secreted by the intraportally transplanted islets of Langerhans in diabetic rats.

MeSH Terms
Adenoma/etiology,pathology Animals Blood Glucose/metabolism Body Weight Carcinoma, Hepatocellular/etiology,pathology Case-Control Studies Cause of Death Cytoplasm/ultrastructure Diabetes Mellitus, Type 2/chemically induced Endoplasmic Reticulum/ultrastructure Immunohistochemistry Islets of Langerhans Transplantation Liver Neoplasms, Experimental/etiology,pathology Male Microscopy, Electron Neoplasm Staging Precancerous Conditions/pathology Rats Rats, Inbred Lew Streptozocin Transforming Growth Factor alpha/analysis
Chemicals
Blood Glucose Transforming Growth Factor alpha Streptozocin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Dombrowski F
Pathologisches Institut, Universität Bonn, Germany.
Bannasch P
Pfeifer U
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1997-03-00
Pages
1071-87
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1857898
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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