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Influence of Human -Interferon on Four Human Osteosarcoma Xenografts in Nude Mice¹

Department of Orthopaedic Surgery, K 54, Huddinge Hospital, S-141 86 Huddinge, Sweden [O. B.]; Department of Orthopaedic Surgery, Karolinska Hospital, Box 60500, S-104 01 Stockholm, Sweden [H. C. F. B., L-Å. B., U. N., O. S. N.]; Department of Pathology, F 42, Huddinge Hospital, S-141 86 Huddinge, Sweden [F. P. R.]; Department of Oncology, Karolinska Hospital, Box 60500, S-104 01 Stockholm, Sweden [H. S.]; and Department of Medical Radiobiology, Box 60400, S-104 01 Stockholm, Sweden [B. T.]

Growth-inhibiting effects of human -interferon (HulFN-) were investigated in four human osteosarcoma xenografts in nude mice. In addition to effects on growth, the HulFN- treatment was evaluated by histological examination and DNA flow cytometric analysis. Daily doses of 2 x 10⁵ IU HulFN- completely arrested the growth of two osteosarcoma xenografts and partially inhibited one, whereas 1 x 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 HulFN--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 cycle time. The modal DNA value of one xenograft was changed from aneuploid to diploid during HulFN- 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 HulFN- can also have a direct antiproliferative effect.

¹ Supported by grants from the Jonas Björnberg Memorial Foundation, the Swedish Children's Cancer Society, and the Stockholm Cancer Society and by Swedish Cancer Society Grant 1841–84. Presented in part at the 1984 TNO-ISIR Meeting on the Biology of the Interferon System, Heidelberg, Germany, October 1984 (1).

² To whom requests for reprints should be addressed, at Department of Orthopaedic Surgery, Karolinska Hospital, Box 60500, S-104 01 Stockholm, Sweden.

Received 1/14/85. Revised 5/ 6/85. Accepted 7/17/85.