INFLUENCE OF HUMAN ALPHA-INTERFERON ON 4 HUMAN OSTEO-SARCOMA XENOGRAFTS IN NUDE-MICE

Growth-inhibiting effects of human .alpha.-interferon (HuIFN-.alpha.) were investigated in four human osteosarcoma xenografts in nude mice. In addition to effect on growth, the HuIFN-.alpha. treatment was evaluated by histological examination and DNA flow cytometric analysis. Daily doses of 2 .times. 105 IU HuIFN-.alpha. completely arrested the growth of two osteosarcoma xenografts and partially inhibited one, whereas 1 .times. 106 IU/day were necessary to arrest the growth of the fourth. Growth inhibition was reversible and tumor size independent. The histological appearance, including mitotic indices, and S-phase proportions were unchanged in three xenografts. The mechanism of the HuIFN-.alpha.-induced growth inhibition of these three xenografts was therefore not considered to be a direct antiproliferative effect, but rather due to increased cell loss and/or increased cell loss and/or increased cell cycle time. The modal DNA value of one xenograft was changed from aneuploid to diploid during HuIFN-.alpha. treatment. Histologically, these xenografts were partly replaced by normal appearing bone and bone marrow. The S-phase proportion was also reduced in these xenografts, implying that HuIFN-.alpha. can also have a direct antiproliferative effect.