Summary
Liver cyst formation was studied serially in an experimental model in which rats were fed a diet containing 0.02% 2-acetylaminofluorene, a carcinogen, for 6 weeks, followed by a normal diet for 42 weeks. Cysts appeared in the portal tracts at the 12th week, by which time the intrahepatic bile ducts had also proliferated and dilated. Some of the dilated bile ducts were cavernous or multicystic and appeared to represent a transitional form between the bile duct dilatation and cystic formation. After 20 weeks cysts were observed in the majority of rats. The number and the size of cysts in the liver increased with time; after 40 weeks, there were up to 20 cysts as large as 15 mm in diameter. Carcinoma or cirrhosis did not develop in this model. Indocyanine green dye injected intravenously did not accumulate in the cysts, which denies the possibility of communication between cysts and the bile duct. Scanning electron microscopy demonstrated that the cysts were composed of a few intercommunicating cavities and were lined with epithelial cells similar to those of the intrahepatic bile duct, which had numerous microvilli and a central cilium. These observations suggest that liver cysts originate in the bile duct.
Similar content being viewed by others
References
Sasaki T. Yoshida T: Experimentelle Erzeugung des Lebercarcinoms durch Fuetterung mit o-Aminoazotoluol. Virchows Arch Pathol Anat 1935;295:175–200
Kinoshita R: Studies on the cancerogenic chemical substances. Trans Scoc Path Jap 1937:27:665–725
Brock N, Druckrey H, Hamperl H: Die Erzeugung von Leberkrebs durch den Farbstoff 4-Dimethylaminoazobenzol. Z Krebsforch 1940;50:431–455
Orr JW: The histology of the rat’s liver during the course of carcinogenesis by butter-yellow (P-dimethylaminoazobenzene). J Path Bact 1940;50:393–408
Edwards JE, White J: Pathologic changes with special reference to pigmentation and classification of hepatic tumors in rats fed p-dimethyl-aminoazobenzene (butter yellow). J Natl Cancer Inst 1941:2:157–183
Opie EJ: The pathogenesis of tumors of the liver produced by butter-yellow. J exp Med 1944;80:231–346
Mulay AS, Firminger HJ: Liver tumors induced in rats by pdimethylaminoazobenzene. J Natl Cancer Inst 1952;13:35–55
Firminger HJ: Histopathology of carcinogenesis and tumors of the liver in the rat. J Natl Cancer Inst 1955;15:1427–1435
Lauber W, Danneberg P: Zur Morphologie de durch p-Dimethylamino-azobenzol erzeugten Leberveraenderungen und Tumoren bei der Ratte. Z Krebsforsch 1956;61:327–345
Magee PN, Barnes JM: The production of malignant primary hepatic tumours in the rat by feeding dimethylnitrosamine. Br J Cancer 1956;10:114–122
Stewart HL, Snell KC: The histopathology of experimental tumors of the liver of the rat. Acta Unio Internat Contra Cancrum 1957;13:770–803
Yamamoto H: Tumorigenesis and cystic lesion of the liver by N-bis(2-hydroxypropyl) nitrosamine in ddY mice. J Toxicol Sci 1985;10:315–321
Peraino C, Fry RJM, Staffelt E, et al: Effects of varying the exposure to phenobarbital on its enhancement of 2-acetylaminofluorene induced hepatic tumorigenesis in the rat. Cancer Res 1973;33:2701–2705
Solt D, Farber E: New Principle for the analysis of chemical carcinogenesis. Nature 1976;263:701–703
Ogawa H, Itoshima T, Ukida M, et al: Scanning electron microscopy of experimentally induced hepatocellular carcinoma. Scanning Electron Microsc 1984;1:359–368
Schoental R, Magee PN;Further observations on the subacute and chronic liver changes in rats after a single dose of various pyrrolizidine (Senecio) alkaloids. J Path Bact 1959;78:471–482
Dontenwill W, Mohr U: Proliferationsfordernde und hemmende Wirkung der Geschlechtshormone bei Behandlung von Goldhamstern mit Carcinogenen. Z Krebsforsch 1961;64:381–389
Smith JCH, Schrier B: Cyst formation in rat liver after intravenous radioactive coloidal gold. Arch Path 1965;80;:641–646
Laqueur GL, Matsumoto H: Neoplasms in female Fischer rats following intraperitoneal injection of methylazoxymethanol. J Natl Cancer Inst 1966;37:217–225
Terracini B, Magee PN, Barnes JM: Hepatic pathology in rats in low dietary levels of dimethylnitrosamine. Br J Cancer 1967;21:559–565
Craddock UK: The effect of N’-nitro-N-nitrosomethylguanidiine on the liver after administration to the rat. Experientia (Basel) 1968;24:1148–1149
Bannasch P, Reiss W: Histogenese und Cytogenese cholangiocellulaerer Tumoren bei Nitrosomorpholin-vergifteten Ratten. Zugleich ein Beitrag zur Morphogenese der Cystenleber. Z Krebsforsch 1971;76:193–215
Grice HC, Moodie CA, Smith DC: The carcinogenic potential of aflatoxin or its metabolites in rats from dams fed aflatoxin pre- and postpartum. Cancer Res 1973;33:262–268
Justrabo E, Martin MS, Michiels R, et al: Experimental gastrointestinal neoplasms and hepatic cysts in rats induced by Nmethyl-N’-nitro-N-nitrosoguanidine. Path Europ 1975;10:61–71
Dominis M, Damjanov I: Cystic cholangiofibrosis of the liver. Arch Geschwulstforsch1977;47:661–669
Richards WL, Pitot HC, Potter VR: Hepatic cyst formation in male rats partially hepatectomized as weanlings during shortterm feeding of 2-acetylaminofluorene. Carcinogenesis 1982;3: 1355–1359
Ohta A: Liver cysts (animal model). Kan Tan Sui 1982;5:757–761 (in Japanese)
Ito T, Itoshima T, Ukida M, et al: Peritoneoscopy of the liver stained by intravenous injection of indocyanine green-experimental and clinical studies. Gastroenterol Jpn 1983;8:593–598
Itoshima T, Ito T, Ukida M, et al: Lack of uptake of indocyanine green and trypan blue by hepatocellular caricnoma. Acta Med Okayama 1983;38:65–69
Murakami T: A revised tannin-osmium method of biological specimens for scanning electron microscopy. Arch Histol Jpn 1974;3:189–193
Farber E: Similarities in the sequence of early histological changes induced in the liver of the rat by ethionine, 2-acetylaminofluorene, and 3-methyl-4-dimethylaminoazobenzene. Cancer Res 1956;16:142–148
Itoshima T, Shimada Y, Murakmi T: Scanning electron microscopy of intrahepatic bile duct. Igaku no Ayumi 1974;90:469–472 (in Japanese)
Itoshima T, Yoshino K, Yamamoto K, et al: Scanning electron microscopy of the bile ductule. Gastroenterol Jpn 1977; 13:48–54
Nakanuma Y, Kurumaya H, Ohta G: Multiple cysts in hepatic hilum and their pathogenesis. Virchows Archiv A 1984;404;341–350
Meyenburg H von: Ueber die Cystenleber. Beitr Path Anat 1918;64:447–537
Melnick PJ: Polycystic liver: analysis of seventy cases. Arch Pathol 1955;59:162–172
Chung EB: Multiple bile-duct hamartomas. Cancer (Philad.) 1970;26:287–296
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mizutani, S., Itoshima, T. & Tsuji, T. Experimental liver cysts induced by 2-acetylaminofluorene. Gastroenterol Jpn 26, 170–176 (1991). https://doi.org/10.1007/BF02811076
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02811076