LONG-TERM INTAKE OF A LOW-CASEIN DIET IS ASSOCIATED WITH HIGHER RELATIVE NK CELL CYTOTOXIC ACTIVITY IN F344 RATS

Earlier studies in our laboratory showed that animals exposed to aflatoxin B-1 (AFB(1)) develop fewer gamma-glutamyl transpeptidase-positive preneoplastic foci and tumors when fed 6% dietary casein than when fed 22% casein during promotion; mechanisms underlying this effect have not been elucidated. We examined natural killer (NK) cell activity, mitogenic responses, and lymphocyte surface antigen profiles in male Fischer 344 rats dosed with AFB(1) or dosing vehicle alone and then fed 6% or 22% casein isocaloric diets for one year. Mean body weights and food intake did not differ significantly among the groups during the study. NK cells purified from peripheral blood of rats fed 6% casein mediated higher specific lysis (p < 0.0001) against YAC-1 target cells than cells obtained from animals fed 22% casein. Mitogenic responses of splenic lymphocytes to concanavalin A and lymphocyte subpopulations, identified by flow cytometry, did not differ significantly among dietary groups. Hepatic tumors were detected in 27% of the 22% casein AFB(1)-treated group and in 6% of animals in the 6% casein AFB(1)-treated group. The association between long-term intake of a 6% casein diet and higher relative NK cell cytotoxic activity suggests a potentially important mechanism that may help protect against the development of hepatocellular tumors. Further study of this mechanism as a causal factor in limiting tumor development is required.