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Inhibitory Effects of D-Glucosamine on the Growth of Walker 256 Carcinosarcoma and on Protein, RNA, and DNA Synthesis¹

Department of Medicine A, Roswell Park Memorial Institute, Buffalo, New York 14203, and Department of Biochemistry, State University of New York at Buffalo, Buffalo, New York 14214

The effectiveness of D-glucosamine as an antitumor agent was tested on both rats and mice bearing transplantable tumors. Continuous tail-vein infusion of 0.42 g of glucosamine/kg/hr over a period of 32 to 36 hr resulted in a high rate of tumor regression in Charles River CD rats bearing i.m. Walker 256 carcinosarcoma (subline M-10). The number of tumor-free rats was dependent on the strain of rat used. Continuous s.c. infusion of glucosamine resulted in about 56% regression of s.c. Sarcoma 180 in mice.

Incorporation of lysine-¹⁴C, uridine-¹⁴C, and thymidine-¹⁴C into surviving tumor slices obtained from tumor-bearing rats treated in vivo with glucosamine showed 75 to 85% inhibition of RNA and DNA synthesis and slight inhibition of protein synthesis. The effect of glucosamine on the incorporation of the precursors was much less in normal tissues than in tumor tissue. The effects of glucosamine on acid-soluble nucleotides in neoplastic tissue were studied. It was found that the pool of UDP-N-acetylhexosamine is increased six-fold in Walker 256 carcinosarcoma in vivo but that the pools of other uridine nucleotides (e.g., UMP, UDP, and UTP) were significantly reduced.

The resistance of rats and mice successfully treated with glucosamine to a second syngeneic tumor graft suggests that glucosamine treatment may interfere with the tumor in such a way as to permit the host to respond successfully to the antigenic makeup of the tumor.

¹ This study was supported in part by American Cancer Society Grant P401, Institutional GRSG Allocation FR-0548-03, USPHS Grant CA08492, and Armed Forces Epidemiological Board Grant MD-2803.

² Present address: Department of Chemistry, Florida State University, Tallahassee, Fla. 32306.

Received 2/19/70. Accepted 8/24/70.

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