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Review
. 2019 Nov:83:102673.
doi: 10.1016/j.dnarep.2019.102673. Epub 2019 Jul 25.

Inflammation-induced DNA damage, mutations and cancer

Jennifer Kay  1 , Elina Thadhani  2 , Leona Samson  3 , Bevin Engelward  2
Affiliations
Review

Inflammation-induced DNA damage, mutations and cancer

Jennifer Kay et al. DNA Repair (Amst). 2019 Nov.

Abstract

The relationships between inflammation and cancer are varied and complex. An important connection linking inflammation to cancer development is DNA damage. During inflammation reactive oxygen and nitrogen species (RONS) are created to combat pathogens and to stimulate tissue repair and regeneration, but these chemicals can also damage DNA, which in turn can promote mutations that initiate and promote cancer. DNA repair pathways are essential for preventing DNA damage from causing mutations and cytotoxicity, but RONS can interfere with repair mechanisms, reducing their efficacy. Further, cellular responses to DNA damage, such as damage signaling and cytotoxicity, can promote inflammation, creating a positive feedback loop. Despite coordination of DNA repair and oxidative stress responses, there are nevertheless examples whereby inflammation has been shown to promote mutagenesis, tissue damage, and ultimately carcinogenesis. Here, we discuss the DNA damage-mediated associations between inflammation, mutagenesis and cancer.

Keywords: Cancer; DNA damage; DNA repair; Inflammation; Mutation.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1.
Figure 1.
Diagram describing the relationship between inflammation and DNA damage and how they contribute to cancer.
Figure 2.
Figure 2.
Many reactive oxygen and nitrogen species are produced or derived from innate immune cells.
Figure 3.
Figure 3.
Products of guanine oxidation. A. Primary nitrosation of guanine leads to an abasic site. Primary oxidation of guanine produces 8oxoG, and oxidation of 8oxoG leads to a variety of secondary oxidation products. B. Rotation of the glycosidic bond allows 8oxoG to mispair with A.
Figure 4.
Figure 4.
Products of DNA deamination and subsequent base mispairing.
Figure 5.
Figure 5.
Products of DNA halogenation
Figure 6.
Figure 6.
Products of DNA alkylation following electrophilic attack by lipid peroxidation products
Figure 7.
Figure 7.
Modes by which single strand breaks may lead to double strand breaks.
Figure 8.
Figure 8.
Base excision repair pathway, homologous recombination pathway, and how BER intermediates may lead to HR
Figure 9.
Figure 9.
Several mechanisms for HR-derived mutations.
Figure 10.
Figure 10.
Pathways leading from a single εA lesion to multiple types of mutations.
Figure 11.
Figure 11.
Expanded paradigm describing relationships between inflammation, DNA damage and cancer
See this image and copyright information in PMC

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