Resistance of Copenhagen rats to hepatocarcinogenesis does not involve T-cell immunity

Previously, we have shown that Copenhagen (Cop) rats are highly resistant, compared with susceptible F344 rats, to the growth of glutathione S-transferase 7-7 (GST 7-7) positive preneoplastic liver lesions following treatment with a modified resistant hepatocyte (RH) protocol. Donryu rats, a strain with a level of susceptibility similar to F344, have a reduced T-cell response compared with the closely related, but highly resistant, DRH rat. Cop and DRH rats share several characteristics in their resistance to preneoplastic liver lesion growth and this study, therefore, was designed to examine whether T-cells play a role in Cop resistance. Cop rats were crossed with an athymic (nude) rat to produce F1s that were then interbred to produce F2 animals, some of which were nude with a partial Cop background. A comparison of the susceptibility of nude F2 animals and their euthymic (non-nude) littermates allowed us to determine what role, if any, T-cells play in Cop resistance. We treated 11 Cop, 11 F344, 19 nude F2s, and 18 non-nude F2s with diethylnitrosamine (DEN), followed 3 weeks later by a modified RH protocol. As expected, F344 rats were highly susceptible, having 41.9 ± 3.3% (mean ± SEM) of their liver section areas occupied by GST 7-7-positive lesions and Cop rats were highly resistant, having only 4.7 ± 1.1% of their liver section areas occupied by lesions. Both nude and non-nude F2s were, like Cop rats, highly resistant (1.8 ± 0.29 and 2.7 ± 0.45%, respectively). These results show that T-cells are unnecessary for Cop rat resistance, or only play a minor role, and that the nude parental strain is also likely to be resistant to the growth of preneoplastic liver lesions.