Analysis of DNA adducts in human samples: acrolein-derived exocyclic DNA adducts as an example

Abstract

Acrolein is an environmental pollutant that is also derived endogenously through lipid peroxidation and protein degradation. The reaction of acrolein with 2'-deoxyguanosine produces exocyclic 1,N(2) -propano-2'-deoxyguanosine (AdG) adducts, mutagenic lesions that play important roles in multistage carcinogenesis processes. Accurate quantification of acrolein-derived DNA adducts is a critical step toward elucidating the mode of action of acrolein carcinogenicity. Exposure of humans to acrolein can occur through the smoking of tobacco and the dietary consumption of oxidized polyunsaturated fatty acids. This review describes the use of (32) P-postlabeling- and MS-based methods for the analyses of acrolein-derived DNA adducts in humans as well as present trends toward improving the sensitivity, specificity, and accuracy of the quantification of trace amounts of DNA adducts in DNA of limited availability.