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A Comparison of the Oncogenicities of 3-Hydroxyxanthine, Guanine 3-N-Oxide, and Some Related Compounds¹

Divisions of Experimental Chemotherapy and Biological Chemistry, Sloan-Kettering Institute for Cancer Research, New York, New York 10021

Assays of the oncogenic N-oxide derivatives of xanthine and guanine, which have now been proven to be 3-hydroxyxanthine and guanine 3-N-oxide, continue to show about equal activities. Parallel titrations at 1.0, 0.5, and 0.1 mg/week for 26 weeks, administered subcutaneously, in female Wistar rats show that, for these conditions, the 50% tumor incidence doses lie between the two lower dose levels, or between a total of 2 and 10 mg of the free bases.

The isomeric 1-hydroxyxanthine elicits a different response. While being administered it induces a severe inflammatory and granulomatous condition, but it leads to only a small incidence of tumors. This, coupled with the confirmed low incidence of tumors from 6-mercaptopurine 3-N-oxide, indicates that the oncogenicity of purine N-oxide derivatives is influenced both by the position of the N-oxide and by other substituents.

Although the assay response to adenine 1-N-oxide has been variable, a sufficient incidence of tumors has been observed to indicate that it is at least a moderately oncogenic purine N-oxide.

The inactivities of the parent purines and of a few other purine derivatives are recorded.

¹ This investigation was supported in part by the National Cancer Institute, Grant No. CA-08748, the Damon Runyon Memorial Fund, DRG-1014, and the Atomic Energy Commission, Contract No. AT[30-1]910. This is Paper XXXII in the series on "Purine N-Oxides." A portion was presented at the 59th Annual Meeting of the American Association for Cancer Research, Atlantic City, N. J., April 1968 (27).

Received 6/10/69. Accepted 7/16/69.

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				G. Stohrer and G. B. Brown Oncogenic Purine Derivatives: Evidence for a Possible Proximate Oncogen Science, March 20, 1970; 167(3925): 1622 - 1624. [Abstract] [PDF]