Mutagenicity of derivatives of the oncogenic purine N-oxides.

Acetoxy esters of purine W-oxides inactivate and induce mutations in Bacillus jwà ̈n/Ã1-transforming DNA. The es ters were the chemical models available for the sulfate es ters believed to be formed in vivo. When metabolic suscep tibilities were taken into consideration, there is a reasonable correlation between the mutagenicity of various acetoxy es ters and the oncogenicity of the parent W-oxide derivatives. The acetoxy esters of 3-hydroxyxanthine and 3-hydroxy-lmethylguanine (both strong oncogens in rats) were the most potent mutagens. The acetoxy ester of 7-hydroxyxanthine was also a strong mutagen. Acetoxy esters of the 7-methyland 8-aza-substituted 3-hydroxyxanthine derivatives, as well as 1-acetoxyadenine, 3-acetoxypurine, and 3-acetoxyhypoxanthine, were weak mutagens or not mutagenic. Most of the 3-acetoxyxanthine-induced mutations spontaneously reverted to wild type. The frequency of reversion was in creased to the greatest extent with ethylmethane sulfonate, but was also increased with the base analogs 2-aminopurine and 5-bromodeoxyuridine. Only a few of the mutations were reverted by frame-shift mutagens. It was concluded that mutation induction in transforming DNA by the acetoxy esters of purine W-oxides occurs by both transition and transversion base-pair substitution.