Purine Base Derivatives as Indicators of Damage to DNA

Abstract

This paper reviews recent progress in the field of DNA adducts. It is focused on purine derivatives as important biological indicators of damage to DNA and a possible diagnostic tool for diagnosis of the cancer risk. Main sites of the attack in purine and pyrimidine bases are pointed out and representative examples are given of the types of compounds and their metabolites, which are capable of binding covalently to DNA. An overview of specific and non-specific methods for the detection and quantification of DNA adducts is given and their advantages and limitations are discussed. The carcinogenic potential of adducts expressed as the DNA adduct level corresponding to the tumorigenic dose (TD₅₀) is structure-dependent, so that both the level of the adducted DNA and the structure of the adduct formed must be taken into account when evaluating carcinogenic risk. The exact identification of structure of DNA adducts found in biological materials should rely on authentic standards. However, preparative methods for the standards of many known DNA adducts remain a challenge for organic chemists.