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.

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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).

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