Ultrasensitive and specific detection methods for exocylic DNA adducts: markers for lipid peroxidation and oxidative stress
- PMID: 11090950
- DOI: 10.1016/s0300-483x(00)00307-3
Ultrasensitive and specific detection methods for exocylic DNA adducts: markers for lipid peroxidation and oxidative stress
Abstract
Among exocyclic DNA adducts, etheno (epsilon) bases (epsilond A, epsilond C, N(2),3-epsilond G) are generated by reactions of DNA bases with lipid peroxidation (LPO) products derived from endogenous sources and from the carcinogens vinyl chloride or urethane. The recent development of ultrasensitive methods has made it possible to detect these epsilon-adducts in vivo and to study their formation and role in experimental and human carcinogenesis. The promutagenic epsilon-DNA modifications can be detected by immunoaffinity/32P-postlabelling or by immunohistochemistry. When epsilon-adducts are excised from tissue DNA, the modified nucleosides can be quantified in urine by an immunoaffinity-HPLC-fluorescence method. Highly variable background levels of epsilon-adducts were detected in tissues from unexposed humans and rodents, suggesting an endogenous pathway of formation from reaction of trans-4-hydroxy-2-nonenal (via its 2,3-epoxide) with DNA bases. Several known cancer risk factors increased the level of these DNA lesions: Elevated epsilon-adducts were found in hepatic DNA from patients with excess metal storage (haemochromatosis, Wilson's disease), resulting in oxidative stress and high risk of liver cancer. Reactive O/N-intermediates generated during inflammatory processes, for example in patients with inflammatory bowel disease (IBD) and familial adenomatous polyposis (FAP) led to the formation of epsilon-adducts likely through peroxynitrite-mediated LPO and/or increased oxidative arachidonic acid metabolism. A high omega-6-polyunsaturated fatty acid (PUFA) diet increased epsilon-DNA adducts in white blood cells (WBC), particularly in female subjects (about 40-fold), while the level of adducted malondialdehyde in deoxyguanosine of WBC-DNA was only moderately elevated. In conclusion, there is now growing evidence that epsilon-adducts were elevated in cancer-prone patients and in rodents (liver, pancreas, colon, skin), suggesting that promutagenic epsilon-adducts, when formed as a consequence of persistent oxidative stress, can drive cells to malignancy. Therefore, biomonitoring of exocyclic DNA adducts offers useful tools: (i) to evaluate the etiological contributions of dietary fats, oxidative stress, and chronic inflammatory/infectious processes; (ii) to verify the efficacy of chemopreventive agents on endogenous DNA damage and cancer risk; and (iii) to gain mechanistic insights into the role of oxidative stress/LPO-derived lesions in the initiation and progression of human cancer.
Similar articles
-
New DNA-based biomarkers for oxidative stress and cancer chemoprevention studies.Eur J Cancer. 2000 Jun;36(10):1229-34. doi: 10.1016/s0959-8049(00)00095-2. Eur J Cancer. 2000. PMID: 10882861 Review.
-
Etheno DNA-base adducts from endogenous reactive species.Mutat Res. 1999 Mar 8;424(1-2):59-69. doi: 10.1016/s0027-5107(99)00008-1. Mutat Res. 1999. PMID: 10064850 Review.
-
Potential role of lipid peroxidation derived DNA damage in human colon carcinogenesis: studies on exocyclic base adducts as stable oxidative stress markers.Cancer Detect Prev. 2002;26(4):308-12. doi: 10.1016/s0361-090x(02)00093-4. Cancer Detect Prev. 2002. PMID: 12430635
-
Lipid peroxidation-induced etheno-DNA adducts in humans.IARC Sci Publ. 1999;(150):55-61. IARC Sci Publ. 1999. PMID: 10626208
-
Oxidative stress and lipid peroxidation-derived DNA-lesions in inflammation driven carcinogenesis.Cancer Detect Prev. 2004;28(6):385-91. doi: 10.1016/j.cdp.2004.07.004. Cancer Detect Prev. 2004. PMID: 15582261 Review.
Cited by
-
Metal-free synthesis of 1,N 6-ethenoadenines from N 6-propargyl-adenines via NIS mediated radical cascade reaction.RSC Adv. 2019 Nov 26;9(66):38897-38901. doi: 10.1039/c9ra09198j. eCollection 2019 Nov 25. RSC Adv. 2019. PMID: 35540232 Free PMC article.
-
Biomarkers of nucleic acid oxidation - A summary state-of-the-art.Redox Biol. 2021 Jun;42:101872. doi: 10.1016/j.redox.2021.101872. Epub 2021 Jan 28. Redox Biol. 2021. PMID: 33579665 Free PMC article.
-
Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action.Int J Environ Res Public Health. 2020 Jan 8;17(2):423. doi: 10.3390/ijerph17020423. Int J Environ Res Public Health. 2020. PMID: 31936320 Free PMC article. Review.
-
Antioxidant and anti-inflammatory medicinal plants have potential role in the treatment of cardiovascular disease: a review.Am J Cardiovasc Dis. 2017 Apr 15;7(2):19-32. eCollection 2017. Am J Cardiovasc Dis. 2017. PMID: 28533927 Free PMC article. Review.
-
The impact of zinc oxide nanoparticles on the bacterial microbiome of activated sludge systems.Sci Rep. 2016 Dec 14;6:39176. doi: 10.1038/srep39176. Sci Rep. 2016. PMID: 27966634 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous
