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Cited by 205Antioxidant Activity and Oxidative StressCarcinogens and Genotoxicity AssessmentRedox biology and oxidative stress

DNA damage by lipid peroxidation products: Implications in cancer, inflammation and autoimmunity

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Gentile, Fabrizio, Arcaro, Alessia, Pizzimenti, Stefania, Daga, Martina, Cetrangolo, Giovanni Paolo, Dianzani, Chiara, Lepore, Alessio, Graf, Maria +2 more·2017·AIMS Genetics
DOI 10.3934/genet.2017.2.103PMC PMC6690246
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Abstract

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity.

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  • 4-HNE results in a low level of interstrand crosslinks.

    “4-HNE has also been shown to result in a low level of interstrand crosslinks, which are the most destructive type of DNA adduct [82].”

    From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [82]

    The HNE section (page not provided) says HNE-derived adducts can form interstrand cross-links and describes these as among the worst kinds of DNA damage. It does not establish that HNE produces a low level of cross-links; it says one HNE-derived adduct is fully converted to a cross-link, while only one of four stereoisomers induces cross-linking. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • 4-HNE adducts can alter DNA base pairing, resulting in stabilized GHNE-A mispairs, which can give rise to G-C→T-A transversion mutations.

    “4-HNE adducts can alter DNA base pairing, resulting in stabilized GHNE-A mispairs, which can give rise to G-C→T-A transversion mutations [82].”

    From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [82]

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Cited by

Sorted by citations

Authors
Gentile, F., Arcaro, A., Pizzimenti, S., Daga, M., Cetrangolo, G. P., Dianzani, C., Lepore, A., Graf, M., Ames, P. R. J., & Barrera, G.
Affiliations
  • University of Molise (IT)
  • University of Turin (IT)
  • University of Naples Federico II (IT)
  • Dumfries and Galloway Royal Infirmary (GB)
Corresponding author
Barrera, Giuseppina
ORCID
Venue
AIMS Genetics
Publisher
Georg Thieme Verlag KG
Published
2017-08
Volume
04
Issue
02
Pages
103-137
ISSN
2377-1143 (ISSN-L)
DOI
10.3934/genet.2017.2.103
PMC
PMC6690246
OpenAlex
W2606713207
Cited by
205
References
4
Citations by year
2026: 22 · 2025: 32 · 2024: 36 · 2023: 30 · 2022: 33 · 2021: 28 · 2020: 16 · 2019: 4 · 2018: 4
FWCI
0.75
Type
journal article
Language
en
Open access
Licence
Locations
  • Global Medical Genetics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca - Università degli Studi del Molise (submittedVersion, cc-by-nc-sa)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
lipid peroxidation, DNA damage, reactive aldehydes, malondialdehyde, acrolein, crotonaldehyde, 4-hydroxynonenal, DNA adducts, oxidative stress, inflammation, autoimmunity, epigenetic modifications, carcinogenesis, mutagenesis, apoptosis, immune tolerance, autoantigens, autoimmune disease pathogenesis

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