Experimental production of osteosarcomas by using 32P and 4 NQO in inbred F 344 rats and their transplantability.

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Even today, few transplantable bone-forming osteosarcomas are available. Therefore, we tried to produce such tumors experimentally in the bone of rats with administration of 4 NQO and/or 32P. The results were as follows: 1) No malignant bone tumor developed in 100 g rats with a single administration of 4 NQO into the mandible and femur in doses of 2 or 4mg per body weight. 2) Combined administration of 32P (2.8μci/g) with 4 NQ0 (0.17-1mg/100g) produced tumors in 77 out of 87 rats. Histologically tumors were classified as osteosarcoma (78.0%), fibrosarcoma (15.8%) and others. The locally inoculated 4 NQO showed less inductivity of osteosarcoma, but increased producing of fibrosarcoma. 3) Several characteristics of induced osteosarcomas were observed: Osteosarcomas with higher ossification had a longer doubling time and a higher incidence of lung metastasis and a higher value of serum alkaline phosphatase were observed. These findings could serve clinical diagnosis and therapy of human osteosarcomas. 4) Three transplantable osteosarcomas (MSU-A 3, -D 16, -E 3) in vivo and one osteosarcoma cell line (MSK) in vitro were established. These strains and one cell line showed a marked osteoid forming activity when they were inoculated subcutaneously into the back of F 344 rats. We believe that these tumors would be very useful as a model of osteosarcomas.
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