Purine N-oxides. XIX. On the oncogenic N-oxide derivatives of guanine and xanthine and a nononcogenic isomer of xanthine N-oxide.

Abstract

Summary The oncogenic N -oxide derivatives of xanthine and guanine are now considered to be primarily the 7-hydroxyxanthine and 7-hydroxyguanine tautomers of the N -oxides. Additional assays of this xanthine derivative at 3, 5, or 7 mg/rat/week have continued to lead to nearly 100% incidence of a variety of tumors at the site of the subcutaneous injection. At a 3-mg dose level the guanine derivative also led to a 100% incidence of tumors at the site, and the two must now be considered equally oncogenic. An isomeric xanthine N -oxide, 3-hydroxyxanthine, has proven inactive, which indicates that considerable structural specificity is required for oncogenicity. At a very high dose level, 6-mercaptopurine 3- N -oxide induced tumors at the site of injection in 3 of 15 rats. The parent purines, xanthine and guanine, as well as adenine, have not induced tumors at the site of injection, but, in a small series of rats, the incidence of tumors elsewhere was slightly higher than the presently known incidence of spontaneous tumors in other controls.