The fingerprints of the host innate immunity on the cells of primary virus-induced tumors.

As shown earlier, the cells transformed in vitro by various oncogenes, during subsequent in vivo growth were gradually replaced by descendant tumor cells, which co-expressed highly increased H(2)O(2)-catabolizing antioxidant activity (H(2)O(2)(CA)), and the ability to release PGE(2) (PGE(S)) in contact with natural killer cells; v-src was the only oncogene, which in vitro induced cells transformation characterised with the expression of [H(2)O(2)(CA)+PGE(S)] phenotype. Expression of [H(2)O(2)(CA)+PGE(S)] phenotype was providing tumor cells with significantly increased resistance to cytotoxic activities of macrophages and NK cells. However, the possible involvement of [H(2)O(2)(CA)+PGE(S)] phenotype in primary carcinogenesis remained obscure. Here, using three models of the primary virus-induced Syrian hamster tumors we demonstrated that Rous Sarcoma Virus-induced tumors arising after short latent period expressed [H(2)O(2)(CA) + PGE(S)] phenotype at appearance. During the latent periods of SV40- and SA7(C8)-induced tumors the cells expressing [H(2)O(2)(CA)+PGE(S)] phenotype gradually replaced the original [H(2)O(2)(CA)+PGE(S)]-phenotype-negative cell populations. The effectiveness of such selection correlated with the duration of in vivo tumor development. Thus it was shown, that selection of tumor cells expressing [H(2)O(2)(CA)+PGE(S)] phenotype is beginning and may be completed during the latent period of primary carcinogenesis. Taken together, data of this and preceding our studies on [H(2)O(2)(CA)+PGE(S)] phenotype demonstrate that in vivo the host innate immunity antitumor reactions are apparently responsible for the selection of rare tumor cell variants capable to defend themselves against CTA of Mph and NK.