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Chemoresponsiveness of Moloney Sarcoma Virus-induced Osteosarcoma to Adriamycin in the Rat¹

Department of Veterinary Pathobiology, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210

The chemoresponsiveness of a Moloney sarcoma virus-induced osteosarcoma in the rat to i.v. Adriamycin therapy was demonstrated by (a) prolongation of life span, (b) reduction in tumor size, and (c) morphological alterations of the neoplasm. Adriamycin was given to groups of osteosarcoma-bearing rats i.v. or i.p. at 2 mg/kg/week for 10 weeks, at 1 mg/kg/week for 10 weeks, and at 1 mg/kg on Monday, Wednesday, and Friday followed by a week of rest (repeated to a total of 10 injections). Rats receiving 1 mg/kg/week had the most consistent response to Adriamycin treatment, with a significant prolongation of life span from 40 through 95 days and a significant decrease in tumor diameter from 7 days through 50 days after the start of treatment. Other Adriamycin regimens also produced a significant increase in life span and a reduction in tumor size, compared to results with rats in the placebo group. Radiographic evaluation of osteosarcomas demonstrated an increased radiodensity with Adriamycin therapy, compared to a rapid proliferation and destruction of preexisting bone in the placebo group. Microscopic and ultrastructural evaluation of osteosarcomas following various intervals of Adriamycin revealed necrosis of tumor cells, fibroblastic proliferation, and mineralization of osteold matrix. Metastatic lesions in lung and sublumbar lymph node also were sensitive to Adriamycin therapy, as reflected by necrosis of tumor cells. Evidence of congestive heart failure and cardiomyopathy was observed in all groups of rats on Adriamycin chemotherapy. The sensitivity of the osteosarcoma-bearing New Zealand black rat to the antitumor and cardiomyopathic effects of Adriamycin provides an animal system for evaluation of the oncolytic activity of new analogs as well as their cardiotoxic potential.

¹ This study was supported in part by NIH Grants GM 1052 and RP 05463 and by Grant IN 160 from the American Cancer Society.

² Recipient of Fellowship CA00549 from the National Cancer Institute. To whom requests for reprints should be addressed, at Department of Veterinary Pathobiology, College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, Columbus, Ohio 43210.

Received 11/16/77. Accepted 3/ 7/78.