The Radiotoxic Effects of S³⁵in Growing Cartilage

Abstract

With the availability of radioactive sulfate, many experiments have been conducted to enhance our biological concept of chondroitin sulfate. It has been shown that the radioactive sulfur of labeled sulfate given to rats is incorporated into chondroitin sulfate and fixed in cartilage (1, 2). It is known that differentiated tumors have a metabolic pattern similar to their tissue of origin. The uptake of S35 by tissue cultures of human cartilage and tumors was studied by Layton (3) to confirm the cartilaginous nature of the growths by in vitro studies. Observations on the uptake of sulfate in human chondrosarcoma in vivo appear to be limited to the two cases studied by Gottschalk (4). He found that S35 was retained at high levels in both primary and metastatic chondrosarcoma, with lesser amounts in the normal cartilage, bone marrow, and other tissues. His autoradiographs indicate maximum concentration in the growing portions of the chondrosarcoma and in the areas containing abundant ground substance. Since the beta radiation of S35 is in the neighborhood of 50 kv, the mean range of the emitted electron will be limited to a radius of 100 µ, with a maximum range of 200 µ, As chondroitin sulfate and therefore radioactive sulfur are deposited in greatest concentrations about chondrocytes, the path of the beta rays is sufficient to include a number of cartilage cell diameters. To date, no evidence of cartilaginous destruction has been shown in the low-dose ranges in which radioactive sulfur has been used in animals. It seems essential, before one considers the use of this radioisotope therapeutically in patients with chondrosarcoma, that evidence of a selective radiotoxic effect in cartilage be demonstrated experimentally. Procedures Experiment I: In order to determine if cartilaginous changes could be produced with sublethal doses of S35, eleven litters of white Osborne Mendel suckling rats, varying in age from three days to two weeks and in weight from 8 to 25 gm., were utilized. The radioactive sulfur solution obtained from Oak Ridge was of high concentration, 72.4 mc/ml., with a low solid content of 1 mg./ml. The S35 was carrier-free, in the form of Na2SO4 in an acidified solution which was neutralized before injection. The amounts of radioactive sulfate injected ranged from a postulated toxic level to a tolerated level as follows: 2.0 mc/gm., 1.0 mc/gm., 0.5 mc/gm., 0.2 mc/gm. to 0.1 mc/gm. of body weight. Litter mates were used in each group of animals and control observations were made with stable sulfate and uninjected mates. The full amount of S35 injected under sterile conditions, intraperitoneally, was less than 1 c.c. in volume. Roentgenograms of the animals were made every two weeks initially and then every month. They were weighed weekly. Three animals which died were studied by radio-autographs and microscopic sections.