Abstract
Lipid peroxidation, initiated by reactive oxygen species or enzymes, originates a variety of electrophiles able to modify biomolecules, including DNA. The best studied lipid peroxidation electrophiles are malondialdehyde, 2-alkenals, 4-hydroxy-2-alkenals, and 4-oxo-2-alkenals. We provide an overview of the DNA adducts formed by these aldehydes, their mutagenic properties, the mechanisms involved in their removal from DNA, their occurrence in vivo, and the associations between their in vivo formation and the carcinogenesis process. The DNA adducts most extensively quantified in carcinogenesis conditions in vivo are the malondialdehyde adducts and the etheno adducts, primarily the unsubstituted etheno adducts, but there is an upward trend in the exploitation of substituted etheno adducts formed by 4-oxo-alkenals in cancer-prone inflammatory conditions. The development of mass spectrometry–based analytical methods has taken advantage of the high sensitivity and high resolution of modern instruments to provide promising advances in a DNA adductomics approach. This approach will expand our view of the endogenous DNA lesions that may be associated with different phases of carcinogenesis and provide useful biomarkers for assessment of disease risk, preventive and treatment interventions, and for diagnosis and prognosis purposes. There is also a need to investigate the relationships between the occurrence of the lipid peroxidation–derived DNA adducts, mutations in critical genes, altered gene expression, and changes in cell signaling, metabolism, and epigenetics. Examination of the global picture of changes and their interrelationships will improve our understanding of the role of lipid peroxidation–derived DNA adducts in carcinogenesis.
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de Melo Loureiro, A.P. (2022). DNA Lesions Induced by Lipid Peroxidation Products in Cancer Progression. In: Chakraborti, S., Ray, B.K., Roychoudhury, S. (eds) Handbook of Oxidative Stress in Cancer: Mechanistic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-15-9411-3_52
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