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Effect of Hydroxylamine (NSC-26250) and Related Compounds on Growth of Transplanted Animal Tumors¹

The effect of hydroxylamine (NSC-26250) and related compounds has been examined on the growth of 11 transplanted mouse tumors, including 3 leukemias, and 1 rat tumor. By the end of therapy hydroxyurea (NSC-32065) and its 1-methyl (NSC-529064) and 1-ethyl (NSC-50840) derivatives retarded the growth of 9 tumors, and hydroxyurethan (NSC-71045; hydroxycarbamic acid ethyl ester) and N,O-diacetyl-N-methyl-hydroxylamine (NSC-529091) were active in 6 and 5 tumors respectively. 1,3-Dihydroxyurea, compd. with p-dioxane [2:1] (NSC-528761) and its 1-methyl derivative (NSC-529327), studied in only 3 and 4 tumors respectively, retarded the growth of all tumors. Five chemicals affected the growth of only 1 or 2 tumors; the other 8 drugs were inactive against the tumors used. Only moderate antitumor effects were shown with most of the drug-tumor combinations. Some of the more active drugs had more pronounced effects against Ridgway osteogenic sarcoma, Ehrlich ascites, and leukemia B82A. Comparison of the structure of congeners of hydroxylamine with their antitumor activity has suggested that the tautomerism of the —CO. NH(OH) group is important in determining the antitumor activity. It is possible that the biologically active form of these drugs is the less stable syn isomer.

¹ Supported by contract SA-43-ph-2445 from the Cancer Chemotherapy National Service Center, National Cancer Institute, USPHS; grants CA-05826 and CA-08748 from the National Cancer Institute; and research grant T45G from the American Cancer Society, Delaware Division.

² Sloan-Kettering Institute for Cancer Research and Sloan-Kettering Division, Graduate School of Medical Sciences, Cornell University Medical College, New York, New York.