Level of Inflammation-Related DNA Adducts in Human Tissues

Formation of DNA adducts is thought to be an initial event of carcinogenesis. Improvement in the performance of liquid chromatography-tandem mass spectrometry (LC/MS-MS) enables us to detect trace amounts of DNA adducts in tissue samples. Recently, the authors carried out a comprehensive analysis of DNA adducts by using LC/MS-MS and found that DNA adducts derived from 4-oxo-2(E)-nonenal (4-ONE) and 4-oxo-2(E)-hexenal (4-OHE) were the major DNA adduct types presented in various human tissues. This chapter describes the level of 4-ONE- and 4-OHE-derived DNA adducts in human tissues, the genotoxicity of the adducts, and their possible relation to inflammation. Inflammation-related DNA adducts produced by 4-ONE and 4-OHE are present ubiquitously in human tissues and are even predominant in some cases. This suggests a possible link between inflammation and cancer. The mechanisms involved in the production of 4-OHE by n-3 PUFAs under inflammation have not yet been well elucidated.