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-transfe rase 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 respo nse compared with the closely related, but highly resistant, DRH rat. Cop a nd DRH rats share several characteristics in their resistance to preneoplas tic liver lesion growth and this study, therefore, was designed to examine whether T-cells play a role in Cop resistance. Cop rats mere crossed with a n 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 compariso n of the susceptibility of nude F2 animals and their euthymic (non-nude) li ttermates allowed us to determine what role, if any, T-cells play in Cop re sistance. 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% (mea n +/- SEM) of their liver section areas occupied by GST 7-7-positive lesion s and Cop rats were highly resistant, having only 4.7 +/- 1.1% of their liv er 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 t o be resistant to the growth of preneoplastic liver lesions.