STUDIES OF THE LATE EFFECTS OF INTERNAL IRRADIATION BY RADIOACTIVE STRONTIUM IN THE RAT

Journal Article · Tue Jan 01 04:00:00 EST 1963 · Laval Medical (Canada)

OSTI ID:4688623

Kahn, D S; Makhani, J S; Skoryna, S C

The late effects of radioactive Sr on bone, the doseresponse relation, and the effects of modifying factors were studied in the rat, which was selected because growth persists iong into adult life in many bones. Thus as bone growth occurs in relation to the epiphysis, an appreciable amount of mineral continues to be deposited in this newly formed bone. Sr/sup 89/ was administered intraperitoneally at monthly intervals in total doses of 4.4 mc/g body wt for a 6- month period. Sixty-three percent of the animals survived the minimal latent period for tumor production. The basic tissue changes observed in bone were: disturbance of osteogenesis, fibrosis of the marrow, cellular proliferation, and tumor formation. These changes occurred to the greatest extent in the metaphyseal region, which represents the area of maximum bone formation; to a lesser degree they could also be found in relation to endosteal and periosteal surfaces. The most extreme fibrotic changes, replacing the normal hematopoietic marrow, occurred in the metaphysis. Fibrosis was of a relatively acellular type, with abundant reticulum fibers and only minimal collagen formation. In the metaphyseal area there was a marked decrease in the number of bony trabeculae, indicating a depression of osteogenesis. Changes secondary to decreased mechanical stability, such as healing microfractures and endosteal and periosteal new bone formation, were also found. Fibrosis observed in these animals possibly was related to the primary effect of irradiation; on the other hand, it may represent merely a repair tissue compensating further lack of bony trabeculae. Foci of cellular proliferation were present in the metaphysis as well as in proximity to endosteal and periosteal surface. In these foci, cells with large hyperchromatic nuclei and mitotic figures (some of them atypical) were almost uniformly present. The principal cells in these groups did not resemble either normal osteoblasts or fibroblasts; some of the larger collections of these cells showed evidence of invasion and destruction of normal structures. Although in all the animals surviving the minimal latent period, on microscopic examination, neoplastic changes were found in their bones, only in 89% were tumors demonstrable grossly or by x-ray studies. Many of these animals had multiple tumors and the majority of them developed pulmonary metastases. The distribution of gross tumors in these animals occurred in the following order of frequency; upper end of tibio-fibula, vertebrae, humerus, femur, and sacrum. No tumors or radiation osteitis were observed during the period of observation in animals which received single injections of doses ranging from 0.001 to 1 mu c Sr/sup 89/ per g body wt. After administration of 2 mu c per g body wt or higher doses, malignant bone tumors were found in some rats which survived for 1 year or longer. However, as the mortality in these groups was high, the incidence of malignant bone tumor formation could not be clearly defined because of variability of survival time. When 5 mu c/g body wt was administered as a single injection, all animals died in the immediate post injectlon period. Other groups received intermittent doses of 0.1 mu c intraperitoneally per g body wt twice weekly for variable periods of time. After 40 injections (total dose 4 mu c/g body wt) the mortality was increased appreciably and tumors were frequent in the surviving animals. The results indicate that a total dose of 5 mu c/g body wt, administered either as a single dose or in repeated injections results in almost 100% mortality. (H.H.D.)

• Research Organization: McGill Univ., Montreal
• NSA Number: NSA-17-027149
• OSTI ID: 4688623
• Journal Information: Laval Medical (Canada), Journal Name: Laval Medical (Canada) Vol. Vol: 34; ISSN LAMEA
• Country of Publication: Country unknown/Code not available
• Language: English

Related Subjects

BIOLOGY AND MEDICINE
BONE MARROW
BONES
CANADA
CARCINOGENESIS
CYTOLOGY
LETHAL DOSE
LUNGS
METASTASES
RADIATION DOSES
RADIATION EFFECTS
RADIATION INJURIES
RADIOSENSITIVITY
RATS
REGENERATION
STRONTIUM 89
SURVIVAL TIME