Experimental studies on malignant fibrous histiocytomas in rats I. Production of malignant fibrous histiocytomas by 4-hydroxyaminoquinoline 1-oxide in bone of fischer 344 strain rats

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Abstract
Malignant fibrous histocytomas (MFHs) were induced by a single injection of 4‐hydroxyaminoquinoline 1‐oxide (4‐HAQO) into periosseous tissue of the tibia or by inserting solid 4‐HAQO into the bone marrow of the tibia of male Fischer 344 rats. Periosseous MFHs were induced by doses of 2 mg and 4 mg of 4‐HAQO per rat in three of 13 (23%) rats and nine of 13 (69%) rats, respectively, at 18 to 27 weeks after treatment. Bone MFHs were induced by doses of 2 mg, 4 mg, and 8 mg of 4‐HAQO per rat in one of 15 (7%) rats, 11 of 18 (61%) rats, and 12 of 14 (86%) rats, respectively, after 18 to 29 weeks. Radiologic examination of bone MFH revealed bone destruction with or without a periosteal reaction, pathologic fracture, and tumor invasion into periosseous soft tissue. The serum alkaline phosphatase levels were elevated in rats with bone MFHs. Histologically, these MFHs were divided into fibrous, giant cell, myxoid, and inflammatory types. The incidence of fibrous MFHs was highest. Lung and inguinal and/or retroperitoneal lymph node metastases were observed in some rats, and these were of the fibrous type. These MFHs were quite similar to those in humans histologically and electron microscopically. This work establishes an animal model for studying the pathogenesis of bone MFH.