SHORT COMMUNICATION: The BN rat strain carries dominant hepatocarcinogen resistance loci

The phylogenetically distant F344 and BN rat strains and their(BNxF344) F1 hybrids were compared for susceptibility to hepatocarcinogenesisusing the ‘resistant hepatocyte’ model. Quantitativestereological analysis of frequency (number/liver) and size(mean volume and volume fraction) of placental form glutathioneS-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 statisticallydifferent. However, mean volume and volume fraction of GST-P-positivelesions were much higher in F344 than in both BN and (BNxF344)F1 rats at any time point, with a difference of up to >10-fold.GST-P-positive lesions exhibited a significantly higher labelingindex and much lower remodeling in male F344 than in BN and(BNxF344) F1 rats. HCCs were present at 54–57 weeks afterinitiation in 77% of male F344 and in no (BNxF344) F1 rats andat 70 weeks HCCs were observed in 100% of male F344 and in 23%of (BNxF344) F1 rats. These results suggest that the BN ratstrain is resistant to hepatocarcinogenesis and that its resistanceis genetically transmitted as a dominant character to F1 hybridsof the BN strain with the F344 susceptible strain.