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Comparison of Antitumor Activities of Pancreatic Ribonuclease and Its Cross-linked Dimer¹

Memorial Sloan-Kettering Cancer Center [G. S. T., R. L. K., I. M. M.] and The Rockefeller University [P. B., G. W., D. W.], New York, New York, 10021

The cross-linked dimer of bovine pancreatic RNase (M.W. 28,000) is significantly more effective than the monomer in inhibiting tumor development in mice when administered i.p. 1 day after inoculation with sarcoma 180J ascites cells. Animals bearing solid tumors were not affected. In AKR/J mice with advanced leukemia, a single i.p. injection of 100 µg of the dimer led to about 50% reduction in the enlarged lymph nodes and the spleen at 24 hr. The half-life of the dimer in the bloodstream has been determined to be 10 min in rats and 6 min in mice, compared to values of 5 and 3.5 min, respectively, for the monomer. Analyses of the tissues of untreated leukemic mice for RNase and RNase inhibitors show that the tumor tissues are not deficient in RNase activity. Considerations of possible mechanisms of action of the dimer indicate that other basic proteins in this size range may merit examination as cytostatic agents toward transformed cells.

¹ This work has been supported in part by National Cancer Institute Grant CA-08748 and General Medical Sciences Grant GM-07256.

Received 5/28/76. Accepted 8/ 9/76.