Direct action of interferon and inducers of interferon on tumor cells in athymic nude mice.

Two interferon-mediated enzyme activities, the protein kinase and pppA (2'p5'A)n synthetase (2-5A synthetase) were used to assess the presence and action of interferon on HeLa tumor cells in athymic nude mice. The protein kinase is manifested by the phosphorylation of endogenous proteins with a molecular weight of 67,000 and 72,000 in mouse and human cells, respectively. Treatment of HeLa tumor-bearing mice with mouse interferon (alpha and beta) resulted in enhanced levels of 2-5A synthetase and protein kinase (Mr 67,000) activities in the spleen and lung while there were no apparent effects on HeLa cells. In these HeLa tumor cells of human origin, the 2-5A synthetase and protein kinase (Mr 72,000) activities were enhanced considerably only after treatment of mice with human fibroblastic (beta) interferon. When HeLa tumor-bearing mice were given injections of polyadenylate-polyuridylate or with polyinosinylate-polycytidylate, then the 2-5A synthetase and the protein kinase activities were enhanced in tumor cells [protein kinase] as well as in the different tissues [protein (Mr 67,000) kinase] of mice since both mouse and human interferons were produced under these conditions. These results indicate a direct action of interferon on homologous tumor cells, and furthermore they indicate that tumor cells in an organism may themselves produce interferon and respond to their own interferon.