Reactions of singlet oxygen (¹O₂) with unsaturated fatty acids, proteins, and DNA have been extensively studied since this activated oxygen species can induce various types of cell damage that are related to aging, cancer and other cytotoxic effects. The thermolysis of hydrophilic naphthalene endoperoxides has been used to generate ¹O₂ and we report in this work some studies related to DNA oxidation using an ionic and a non-ionic water-soluble endoperoxides. The recent development of a water soluble naphthalene endoperoxide acting as a chemical source of [¹⁸O] isotopically labeled singlet oxygen (¹⁸[¹O₂]) is described. Using this approach, advances in ¹O₂ oxidation of DNA have been contributed to elucidate mechanism features of ¹O₂ reaction towards this biological target, since the product formed is labeled and can be detected and quantified using appropriate methods like HPLC coupled to mass spectrometry.