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Furan-Induced Hepatic Cholangiocarcinomas in Fischer 344 Rats

National Toxicology Program, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709

Herschell D. Giles

Southern Research, P.O. Box 55305, Birmingham, Alabama 35255

Donald J. Dykes

Southern Research, P.O. Box 55305, Birmingham, Alabama 35255

Richard D. Irwin

National Toxicology Program, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, North Carolina 27709

In a 2-yr carcinogenicity bioassay, 0, 2, 4, or 8 mg furan/kg body weight (BW) was administered to male and female Fischer (F344) rats and resulted in an 86-100% incidence of cholangiocarcinomas with occasional metastasis. In a separate but concurrent study, male F344 rats dosed with 30 mg furan/kg BW for 90 days developed marked cholangiofibrosis and cholangiohepatitis and, when subsequently maintained without further treatment for an additional 6, 12, or 18 months, the cholangiofibrosis progressed to yield a 100% incidence of cholangiocarcinomas. Transplantation of 21 primary cholangiocarcinomas into syngeneic recipients resulted in growth from 4 donors. The 4 transplanted lines were successfully transferred through 8 serial passages and resulted in metastases in the recipients. The progressive growth of these proliferative hepatocholangial lesions over time, their transplantability, and the development of metastases in some of the cases provide biological evidence of the malignant potential of the furan-induced liver changes.

Key Words: Cholangiohepatitis • hepatocarcinogenesis • transplantation • tumor progression • "stop study"

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Toxicologic Pathology, Vol. 19, No. 4-2, 561-570 (1991)
DOI: 10.1177/019262339101900401


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Maronpot, R. R. Articles by Irwin, R. D. Search for Related Content PubMed PubMed Citation Articles by Maronpot, R. R. Articles by Irwin, R. D. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB FURAN Social Bookmarking                         What's this?