Pascale, Rosa Maria and Simile, Maria Maddalena and De Miglio, Maria Rosaria and Muroni, Maria Rosaria and Gaspa, Leonardo and Dragani, Tommaso A. and Feo, Francesco (1996) The BN rat strain carries dominant hepatocarcinogen resistance loci. Carcinogenesis, Vol. 17 (8), p. 1765-1768. ISSN 1460-2180. Article.
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The phylogenetically distant F344 and BN rat strains and their (BNXF344) F1 hybrids were compared for susceptibility to hepatocarcinogenesisusing the ‘resistant hepatocyte’ model. Quantitative stereological analysis of frequency (number/liver) and size (mean volume and volume fraction) of placental form glutathione S-transferase (GST-P)-positive lesions was carried out at 8, 15 and 32 weeks after diethylnitrosamine initiation. The number/liverof GST-P-positive lesions at any time point was slightly higherin BN and (BNXF344) F1 rats than in F344 rats, but not statistically different. However, mean volume and volume fraction of GST-P-positive lesions were much higher in F344 than in both BN and (BNXF344) F1 rats at any time point, with a difference of up >10-fold. GST-P-positive lesions exhibited a significantly higher labeling index and much lower remodeling in male F344 than in BN and (BNXF344) F1 rats. HCCs were present at 54-57 weeks after initiation in 77% of male F344 and in no (BNXF344) F1 rats and at 70 weeks HCCs were observed in 100% of male F344 and in 23% of (BNXF344) F1 rats. These results suggest that the BN rat strain is resistant to hepatocarcinogenesis and that its resistance is genetically transmitted as a dominant character to F1 hybrids of the BN strain with the F344 susceptible strain.
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