Major alterations in the nucleotide structure of DNA in cancer of the female breast.

Abstract

DNA of invasive ductal carcinomas from five women was analyzed for structural alterations in the purine nucleotides using gas chromatography-mass spectrometry with selected ion monitoring. The results were compared to those for a normal DNA control. The carcinoma DNA showed dramatically higher concentrations of the base modifications 8-hydroxy-guanine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, and 8-hydroxyadenine. For example, the concentration of total identified base modifications represented a more than 9-fold increase over the control value. Base modifications of this type, which arise from radical-induced hydroxylation and cleavage reactions of the purine ring, likely play a major role in initiation and probably contribute to the further transformation of neoplastic cells in cancer of the female breast.