Environmental and genetic factors determine the level of NK activity of nude mice and affect their suitability as models for experimental metastasis.

In these studies we have evaluated the effects of age, genetic background, and housing conditions on the NK-cell activity of nude mice measured in vitro and resistance to tumor metastasis in vivo. BALB/cAnN nude mice exhibited lower levels of NK-cell-mediated cytotoxicity than age-matched N:NIH(S) nude mice maintained under similar housing conditions. The stronger response of N:NIH(S) nude mice was observed also after experimental activation of NK cells by Corynebacterium parvum. Nude mice maintained under barrier conditions have weaker NK-cell activity than mice maintained under conventional conditions. The incidence of experimental pulmonary metastases of allogeneic tumors injected into nude mice was inversely correlated with the levels of NK-cell-mediated cytotoxicity. Thus, 3-week-old BALB/cAnN nude mice raised under barrier conditions were more sensitive to development of experimental metastasis than age-matched N:NIH(S) nude mice maintained under barrier conditions or nude mice of either strain maintained under conventional conditions. In both strains, however, the relative differences in metastatic potential among the tumor cell lines observed in syngeneic recipients were maintained. We conclude that young BALB/cAnN nude mice raised under barrier conditions may provide a valuable in vivo model for studying metastasis of neoplasms.