DNA Base Damage Generated in Vivo in Hepatic Chromatin of Mice Upon Whole Body γ-irradiation

Abstract

DNA base lesions in hepatic chromatin formed upon whole-body irradiation of mice were studied. After γ-irradiating (20–470 Gy) and killing animals, chromatin was isolated from their livers and analysed by GC-MS. Five pyrimidine- and five purine-derived DNA lesions were identified and quantified. These were 5-hydroxy-5-methylhydantoin, 5-hydroxycytosine, 5-(hydroxymethyl)uracil, 4,6-diamino-5-formamidopyrimidine, 7,8-dihyro-8-oxoadenine, 2-hydroxyadenine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, 7,8-dihydro-8-oxoguanine, thymine glycol and 5,6-dihydroxyuracil. Except for the latter two, the amounts of these compounds were increased significantly over control levels in the dose range of 100–470 Gy. Above 200 Gy, a deviation from linearity was observed, although the yields were increased in most cases up to 470 Gy. The modified bases that were identified are typically produced by hydroxyl radical attack on the DNA bases. This may indicate a role for hydroxyl radicals in their formation in vivo. These lesions may play a role in the biological consequences of ionizing radiation such as mutagenesis and carcinogenesis.