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Toxicologic Pathology
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Journal Article

Abnormalities in Liver Iron Accumulation During N-2-Fluorenylacetamide Hepatocarcinogenesis that are Dependent or Independent of Continued Carcinogen Action

Keizo Furuya

Naylor Dana Institute for Disease Prevention, American Health Foundation, Dana Road, Valhalla, NY 10595

Yoshiichi Maeura

Naylor Dana Institute for Disease Prevention, American Health Foundation, Dana Road, Valhalla, NY 10595

Gary M. Williams

Naylor Dana Institute for Disease Prevention, American Health Foundation, Dana Road, Valhalla, NY 10595

The characteristics of liver iron accumulation were studied during N-2-fluorenylacetamide (FAA)-induced hepatocarcinogenesis in rats. After injection of iron-dextran in control rats, hepatocytes accumulated stainable iron evenly throughout hepatic lobules. During the feeding of FAA, iron accumulation was reduced in the midzonal and centrilobular regions. After FAA removal, hepatocytes in these regions again accumulated high amounts of iron. Hepatocellular altered foci induced by FAA displayed rather uniform (> 94%) iron-exclusion during FAA feeding. After FAA removal, however, iron-exclusion was lost in a fraction of the foci, while others (40-64%) remained resistant to iron accumulation. A large majority of liver neoplasms (> 93%) displayed resistance to cellular iron accumulation both during FAA feeding and after removal of FAA. Thus, iron-exclusion by liver neoplasms is carcinogen-independent and irreversible, in contrast with that of normal hepatocytes which is completely carcinogen-dependent and reversible. Altered foci appear to represent two populations: one is characterized by reversible iron-exclusion whereas the other, like neoplasms, possesses permanent iron-exclusion.

Toxicologic Pathology, Vol. 12, No. 2, 136-142 (1984)
DOI: 10.1177/019262338401200204
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Home page
 Toxicol PatholHome page
S. Numoto, T. Tanaka, and G. M. Williams
Morphologic and Cytochemical Properties of Mouse Liver Neoplasms Induced by Diethylnitrosamine and Promoted by 4,4'-Dichlorodiphenyltrichloroethane, Chlordane, or Heptachlor
Toxicol Pathol, June 1, 1985; 13(4): 325 - 334.
[Abstract] [PDF]