Etheno (epsilon) modified
DNA bases (epsilond A, epsilond C, epsilond G) are generated from the
carcinogens vinyl chloride and
urethane, but also by reactions of
DNA with products derived from lipid peroxidation (LPO) and oxidative stress via endogenous pathways. Recently developed ultrasensitive methods allowed the detection of these epsilon-adducts in vivo and their role to be studied in experimental and human
carcinogenesis. Highly variable background levels of epsilon-adducts were detected in
DNA from different organs of unexposed humans and rodents. Several known
cancer risk factors increased the level of these DNA lesions in target organs: elevated epsilon-adducts were found in hepatic
DNA from patients with
metal storage diseases, after overproduction of
nitric oxide (NO) by inducible
NO synthase (iNOS) in a mouse model, and in
colonic polyps of
familial adenomatous polyposis patients. A high omega-6-polyunsaturated
fatty acid diet increased epsilon-
DNA adducts in white blood cells of female subjects. In conclusion, epsilon-adducts were found to be elevated in
cancer-prone tissues, suggesting that these promutagenic lesions could drive cells to
malignancy. Therefore, exocyclic
DNA adducts offer new tools in
cancer aetiological research and in verifying the efficacy of chemopreventive agents.