A comparison of the oncogenicities of 3-hydroxyxanthine, guanine 3-N-oxide, and some related compounds.

Abstract

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.