Antitumoral action of interferon and poly(A)poly(U) on HeLa xenografts in the nude mouse.

The mechanism of the antitumoral action of interferon was investigated in athymic Nude mice grafted with HeLa tumour cells. Treatment of such mice with either mouse interferon, human interferon, a mixture of human and mouse interferon or an inducer of interferon, poly(A)poly(U), resulted in inhibition of tumour growth. The most significant inhibition was observed in mice treated with the mixture of the interferons or with poly(A)poly(U). The antitumoral action of interferon is probably mediated by two mechanisms, one which acts directly on tumour cells and another which acts indirectly by activation of one or several systems of the host. In the present study, the level of 2-5A synthetase in the tumour and the natural killer (NK) activity of splenic cells were used as markers to assess the direct and indirect actions of interferon, respectively. We provide evidence to suggest that both mechanisms are active in the antitumoral action of interferon. Enhanced levels of pppA(2'p5'A)n synthetase (2-5A synthetase) in the tumour after treatment with human interferon or poly(A)poly(U) provides biochemical evidence that interferon interacts with tumour cells in an organism (direct action of interferon). Enhanced levels of splenic NK cell activity as a result of injection or production of homologous interferon confirm the activation of the host's defense mechanisms (indirect action of interferon).