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Induction of Osteosarcomas and Hematopoietic Neoplasms by ⁵⁵Fe in Mice¹

Kantonsspital Luzern, Institute of Pathology, 6000 Lucerne, Switzerland [J. A. L.]; Department of Physiology, Mt. Sinai School of Medicine of the City University of New York, New York, New York 10029 [H. B.]; and Medical Research Center, Brookhaven National Laboratory, Upton, Long Island, New York 11973 [E. P. C., U. R.]

Young, adult, female C57BL/6J mice received a single injection of ⁵⁵FeCl₃ of high specific activity or equivalent amounts of cold iron. The animals were kept for duration of life to study late effects of ⁵⁵Fe. The strain was selected because of known low tumor incidence and long life expectancy. The median survival times were 27, 117, and 439 days after treatment with 2.8, 1.4, and 0.7 mCi per mouse, respectively, and thus were inversely related to dose. Median survival in controls was more than 700 days. No tumors occurred in mice that survived less than 300 days. Six osteosarcomas developed in 14 mice that survived ⁵⁵Fe treatment for more than 300 days. In addition, six other neoplasms were diagnosed: two leukemias, two thymic lymphomas, one hemangioendothelioma, and one reticulum cell neoplasm. Control mice had not reached their median survival time by Day 700 after treatment, and the only tumor noted was a reticulum cell neoplasm.

Radioiron was autoradiographically demonstrated in bone surfaces, bone marrow macrophages, and endosteal cells. Since osteosarcoma is believed to originate from the endosteum, it is conceivable that deposition within the target cell of ⁵⁵Fe with its precisely located Auger electron radiation was instrumental in inducing neoplasms. Thus, identification of the cell at risk may be possible. Alternatively, but not exclusively, sufficient radiation for tumor induction may have been accumulated by the X-ray component of bone surface-seeking ⁵⁵Fe.

¹ Research supported by the United States Energy Research and Development Administration and by NIH Grants HL 15685-03 and R01 15237-02. The research described in this paper involved animals maintained in animal care facilities fully accredited by the American Association for Accreditation of Laboratory Animal Care.

² To whom requests for reprints should be addressed.

³ Scholar of the Leukemia Society of America, Inc.

Received 9/ 3/76. Accepted 7/ 1/77.