Furan-Induced Hepatic Cholangiocarcinomas in Fischer 344 Rats

Abstract

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.