N-nitroso-2-acetylaminofluorene: a direct-acting carcinogen inducing hepatocellular carcinoma in Sprague-Dawley rats.
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.
Ho
Y S
YS
Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei, Republic of China.
Lin
J K
JK
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives* / Q000633:toxicity; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000032:analysis; D005982:Glutathione Transferase / Q000032:analysis; D006965:Hyperplasia; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009336:Necrosis; D009603:Nitroso Compounds / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000097:blood
D015415:Biomarkers; D002273:Carcinogens; D009603:Nitroso Compounds; C057157:N-nitroso-N(2)-fluorenylacetamide; D015073:2-Acetylaminofluorene; D005979:Glutathione Peroxidase; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase