N-nitroso-2-acetylaminofluorene: a direct-acting carcinogen inducing hepatocellular carcinoma in Sprague-Dawley rats.

Abstract

To compare the hepatotoxicity and hepatocarcinogenicity of N-nitroso-2-acetylaminofluorene (NO-AAF) and its parent compound, 2-acetylaminofluorene (AAF), male Sprague-Dawley rats were given intraperitoneal (i.p.) or subcutaneous (s.c.) injections of AAF or NO-AAF (60 mg/kg body weight/week) for ten months. In the AAF group, morphological changes were produced which involved gross distortions of the liver with multiple nodule formations. The rat livers in the NO-AAF group appeared to be smooth with a blunt-thick superior segment of the lateral lobe. The serum gamma-glutamyl transpeptidase activity in both the AAF group and the NO-AAF group was significantly elevated (P < 0.0005). The present study shows that i.p. and s.c. injections of NO-AAF resulted in a high incidence of well-differentiated hepatocellular carcinomas (HCC) (7/9 and 4/6, respectively), while poorly differentiated HCCs were induced by i.p. or s.c. administration of AAF (6/9 or 2/6, respectively). Subcutaneous lesions consisting of an inflammatory reaction and fibroadenoma formation were observed in the NO-AAF-treated rats, whereas no such skin lesions were detected in the AAF-treated animals. These results suggest that NO-AAF is a new direct-acting carcinogen which may be useful for investigating hepatocarcinogenesis.

• Authors: Y S Ho, J K Lin
• Journal: Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 85 Issue 8 Pg. 794-800 (Aug 1994) ISSN: 0910-5050 [Print] Japan
• PMID: 7928624 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Carcinogens
• Nitroso Compounds
• N-nitroso-N(2)-fluorenylacetamide
• 2-Acetylaminofluorene
• Glutathione Peroxidase
• gamma-Glutamyltransferase
• Glutathione Transferase
• Aspartate Aminotransferases
• Alanine Transaminase

Topics

• 2-Acetylaminofluorene (analogs & derivatives, toxicity)
• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Biomarkers (analysis, blood)
• Body Weight (drug effects)
• Carcinogens (toxicity)
• Glutathione Peroxidase (analysis)
• Glutathione Transferase (analysis)
• Hyperplasia
• Liver (drug effects, enzymology, pathology)
• Liver Neoplasms, Experimental (chemically induced, pathology)
• Male
• Necrosis
• Nitroso Compounds (toxicity)
• Organ Size (drug effects)
• Rats
• Rats, Sprague-Dawley
• Time Factors
• gamma-Glutamyltransferase (blood)