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Primary Tumors of Bone and Lung in Rats Following Local Deposition of Cupric-chelated N-Hydroxy-2-acetylaminofluorene

Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20014

The deposition of 14.2 mg of cupric-chelated N-hydroxy-2-acetylaminofluorene in the intramedullary cavity of the right femur and 12.6 mg of nonchelated N-hydroxy-2-acetylaminofluorene in the intramedullary cavity of the left femur of 10- to 16-week-old female Osborn-Mendel rats resulted in embolism of the compounds to the lungs in 12 of 32 rats and the development of epidermoid neoplasms in the lungs of 3 of 29 rats that survived. Twenty-eight sarcomas developed at the site of injection of the cupric chelate in 21 of the 29 rats during an observation period of 55 weeks; only one rat developed sarcomas at the site of injection of the nonchelated compound. Three of the 28 tumors were rhabdomyosarcomas; an additional 3 giant-cell sarcomas were presumed to be extraosseous in origin. Twenty-two tumors in 17 rats were composed of either bone-forming or bone marrow elements. Nine of the tumors were predominantly of osteogenic cells, two of chondrogenic cells, one of fibrogenic cells, four of reticulum cells, two of plasma cells, and four of vasoformative tissues. However, many of these tumors contained more than one type of neoplastic cell. Of note were four tumors composed of mixtures of reticular tissues and three tumors composed of both osteogenic and vasoformative neoplastic cells. These complexities of structure and behavior simulated well the characteristics of the bone tumors of man.

Received 11/10/66. Accepted 1/ 9/67.