Strategies for the evaluation of DNA damage and repair mechanisms in cancer

Figueroa‐González, Gabriela; Pérez‐Plasencia, Carlos

doi:10.3892/ol.2017.6002

Cited by 87 publications

(39 citation statements)

References 84 publications

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“…Surprisingly, DNA damage tended to be distributed in the peripheral pulmonary zone while the airway epithelium displayed inappreciable damage effects. Given that the TUNEL assay is limited in its sensitivity and specificity in detecting DNA damage following apoptosis [ 30 ], we used other assays in the following steps to further confirm the effects.…”

Section: Resultsmentioning

confidence: 99%

Unrepaired DNA damage in macrophages causes elevation of particulate matter- induced airway inflammatory response

Luo

Bao

et al. 2018

Aging

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The inflammatory cascade can be initiated with the recognition of damaged DNA. Macrophages play an essential role in particulate matter (PM)-induced airway inflammation. In this study, we aim to explore the PM induced DNA damage response of macrophages and its function in airway inflammation. The DNA damage response and inflammatory response were assessed using bone marrow–derived macrophages following PM treatment and mouse model instilled intratracheally with PM. We found that PM induced significant DNA damage both in vitro and in vivo and simultaneously triggered a rapid DNA damage response, represented by nuclear RPA, 53BP1 and γH2AX foci formation. Genetic ablation or chemical inhibition of the DNA damage response sensor amplified the production of cytokines including Cxcl1, Cxcl2 and Ifn-γ after PM stimulation in bone marrow–derived macrophages. Similar to that seen in vitro, mice with myeloid-specific deletion of RAD50 showed higher levels of airway inflammation in response to the PM challenge, suggesting a protective role of DNA damage sensor during inflammation. These data demonstrate that PM exposure induces DNA damage and activation of DNA damage response sensor MRN complex in macrophages. Disruption of MRN complex lead to persistent, unrepaired DNA damage that causes elevated inflammatory response.

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Section: Resultsmentioning

confidence: 99%

Unrepaired DNA damage in macrophages causes elevation of particulate matter- induced airway inflammatory response

Luo

Bao

et al. 2018

Aging

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“…One major limitation of this study is that we did not directly examine DNA repair. Although analyzing the expressions of DNA repair enzymes as well as performing the OxyBlot study showed how BER was altered within the cells upon cigarette-smoke exposure and lycopene treatment, we admit that extra assays (i.e., comet assay and direct ROS quencher assay [54]) are warranted to further validate the antioxidative efficacy of lycopene in the cells exposed to smoke. These assays will be included in our future direction.…”

Section: Discussionmentioning

confidence: 97%

Lycopene Protects against Smoking-Induced Lung Cancer by Inducing Base Excision Repair

et al. 2020

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Background: Oxidative stress plays a critical role in lung cancer progression. Carotenoids are efficient antioxidants. The objective of this study was to explore the efficacy of all-trans retinoic acid (ATRA) and carotenoids in cigarette smoke-induced oxidative stress within A549 human lung cancer epithelial cells. Methods: A549 cells were pretreated with 1-nM, 10-nM, 100-nM, 1-μM and 10-μM ATRA, β-carotene (BC) and lycopene for 24 h, followed by exposure to cigarette smoke using a smoking chamber. Results: The OxyBlot analysis showed that smoking significantly increased oxidative stress, which was inhibited by lycopene at 1 nM and 10 nM (p < 0.05). In the cells exposed to smoke, lycopene increased 8-oxoguanine DNA glycosylase (OGG1) expression at 1 nM, 10 nM, 100 nM, and 1 μM (p < 0.05), but not at 10 μM. Lycopene at lower doses also improved Nei like DNA glycosylases (NEIL1, NEIL2, NEIL3), and connexin-43 (Cx43) protein levels (p < 0.05). Interestingly, lycopene at lower concentrations promoted OGG1 expression within the cells exposed to smoke to an even greater extent than the cells not exposed to smoke (p < 0.01). This may be attributed to the increased SR-B1 mRNA levels with cigarette smoke exposure (p < 0.05). Conclusions: Lycopene treatment at a lower dosage could inhibit smoke-induced oxidative stress and promote genome stability. These novel findings will shed light on the molecular mechanism of lycopene action against lung cancer.

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“…Previous detection methodologies implemented to sense DNA lesions are based on bulk measurements that only provide information on the damage frequency, but not their specific site location along the DNA strands 33,34 . Furthermore, the idea of using high-fidelity sequencing technologies has recently been considered as an additional way to detect DNA-nicks.…”

Section: Introductionmentioning

confidence: 99%

Interaction dynamics and site-specific electronic recognition of DNA-nicks with 2D solid-state nanopores

2020

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Single-stranded breaks in the DNA backbone caused by many endogenous and exogenous agents often lead to double-stranded breaks that are known causes of chromosomal instabilities leading to copious diseases. We describe a label-free detection technique using two-dimensional (2D) solid-state nanopore field-effect transistors (FETs) to sense and map site-specific nicks in the DNA backbone. We use all-atom molecular dynamics simulations coupled with electronic transport modeling to illustrate the 2D membrane device capability to sense minute structural changes of any translocating biomolecules via their in-plane electronic sheet current signatures, whereas Van der Waals analyses explain the distinct hydrophobic interactions between various DNA-nick types with graphene and MoS2 nanopore membranes. Specifically, we describe the atypical unzipping behavior of DNA strands caused by the biomolecule sticking at nicked site in the graphene nanopore, under the influence of voltage-specific translocations.

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Strategies for the evaluation of DNA damage and repair mechanisms in cancer

Cited by 87 publications

References 84 publications

Unrepaired DNA damage in macrophages causes elevation of particulate matter- induced airway inflammatory response

Unrepaired DNA damage in macrophages causes elevation of particulate matter- induced airway inflammatory response

Lycopene Protects against Smoking-Induced Lung Cancer by Inducing Base Excision Repair

Interaction dynamics and site-specific electronic recognition of DNA-nicks with 2D solid-state nanopores

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