This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Brown, G. B. Articles by Cresswell, R. M. Search for Related Content PubMed PubMed Citation Articles by Brown, G. B. Articles by Cresswell, R. M.

Purine N-Oxides

XVI. Oncogenic Derivatives of Xanthine and Guanine¹

( Division of Biological Chemistry and the Division of Experimental Chemotherapy, Sloan-Kettering Institute for Cancer Research; Sloan-Kettering Division, Graduate School of Medical Sciences, Cornell University Medical College, New York, New York)

The oxidation of guanine to an N-oxide and its hydrolysis to a xanthine N-oxide are reported.

The s.c. administration of the xanthine N-oxide to rats for 6 months resulted in development of a variety of tumors. There were 1 liposarcoma, 3 fibrosarcomas, 1 mammary adenocarcinoma, 3 fibroblastic tumors, 2 rhabdomyosarcomas, and 1 epidermoid carcinoma at the site of injection and elsewhere in 11 out of 13 rats, or an incidence of 85%. The 1st measurable tumor appeared at 230 days and the last at 442 days after the 1st injection of the compound.

The guanine N-oxide, injected s.c. for 6 months, but at a lower concentration, induced 2 fibrosarcomas and 2 fibroblastic tumors in 15 rats; the 1st tumor appeared at 334 days and the last at 445 days after the 1st injection of the compound.

Administration of adenine 1-N-oxide for 6 months failed to produce tumors in any tissues of 13 rats during the experimental period of 15 months.

Of 8 tumors induced by the xanthine N-oxide, 7 were transplantable, and serial transmission has been successful for 15 generations with one fibrosarcoma and for 5 generations with another.

¹ This work has been supported in part by funds from the National Cancer Institute, NIH, USPHS (CA-03190), the Cancer Chemotherapy National Service Center (Contract SA-43-ph-2445), and the Atomic Energy Commission (Contract No. AT[30-1]-910).

² Present address: Wellcome Research Laboratories, Tuckahoe, N. Y.

Received 2/12/65.