CoChat
Sign Up
Cited by 44DNA Repair MechanismsCarcinogens and Genotoxicity AssessmentSmoking Behavior and Cessation

NEIL2 protects against oxidative DNA damage induced by sidestream smoke in human cells

Open access
Sarker, Altaf H., Chatterjee, Arpita, Williams, Monique, Lin, Sabrina, Havel, Christopher, Jacob III, Peyton, Boldogh, Istvan, Hazra, Tapas K. +2 more·2014·PLoS ONE
DOI 10.1371/journal.pone.0090261PMC PMC3945017
Open this paper in CoChat — free accountOpen PDF

Abstract

Secondhand smoke (SHS) is a confirmed lung carcinogen that introduces thousands of toxic chemicals into the lungs. SHS contains chemicals that have been implicated in causing oxidative DNA damage in the airway epithelium. Although DNA repair is considered a key defensive mechanism against various environmental attacks, such as cigarette smoking, the associations of individual repair enzymes with susceptibility to lung cancer are largely unknown. This study investigated the role of NEIL2, a DNA glycosylase excising oxidative base lesions, in human lung cells treated with sidestream smoke (SSS), the main component of SHS. To do so, we generated NEIL2 knockdown cells using siRNA-technology and exposed them to SSS-laden medium. Representative SSS chemical compounds in the medium were analyzed by mass spectrometry. An increased production of reactive oxygen species (ROS) in SSS-exposed cells was detected through the fluorescent detection and the induction of HIF-1α. The long amplicon-quantitative PCR (LA-QPCR) assay detected significant dose-dependent increases of oxidative DNA damage in the HPRT gene of cultured human pulmonary fibroblasts (hPF) and BEAS-2B epithelial cells exposed to SSS for 24 h. These data suggest that SSS exposure increased oxidative stress, which could contribute to SSS-mediated toxicity. siRNA knockdown of NEIL2 in hPF and HEK 293 cells exposed to SSS for 24 h resulted in significantly more oxidative DNA damage in HPRT and POLB than in cells with control siRNA. Taken together, our data strongly suggest that decreased repair of oxidative DNA base lesions due to an impaired NEIL2 expression in non-smokers exposed to SSS would lead to accumulation of mutations in genomic DNA of lung cells over time, thus contributing to the onset of SSS-induced lung cancer.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0090261

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The skin from THS-exposed mice exhibits higher levels of 8-OH-dG detected by TBARS and LA-qPCR assays.

    “These results indicate that THS exposure causes increased levels of oxidative DNA damage in the mouse skin tissues, which is consistent with the observation that the skin from the same exposed mice exhibit higher levels of 8-OH-dG detected by both the TBARS and LA-qPCR assays [55].”

    From Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing (2016) · cites this paper as [55]

    The Discussion (page unavailable) reports increased oxidative DNA damage measured by the same technique in human cells exposed to thirdhand smoke. The cited paper does not report a finding in mouse skin, or higher 8-OH-dG levels detected by both TBARS and LA-qPCR; its own LA-qPCR experiments used human cells exposed to sidestream smoke. (LLM, conf=0.81)

    Experimental — accuracy not yet measured

  • THS exposure causes increased levels of oxidative DNA damage in mouse skin tissues.

    “These results indicate that THS exposure causes increased levels of oxidative DNA damage in the mouse skin tissues, which is consistent with the observation that the skin from the same exposed mice exhibit higher levels of 8-OH-dG detected by both the TBARS and LA-qPCR assays [55].”

    From Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing (2016) · cites this paper as [55]

    The Discussion reports increased oxidative DNA damage after thirdhand-smoke exposure in human BEAS-2B cells. It also mentions damage in mouse lung, heart and liver after sidestream-smoke exposure, but does not report thirdhand-smoke exposure or 8-OH-dG measurements in mouse skin. The cited paper therefore supports the general link between smoke exposure and oxidative DNA damage, not the mouse-skin finding attributed to it. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 34

  1. [1]Centers for Diseases Control and Prevention (2010) Vital Signs: Nonsmokers Exposure to Secondhand Smoke-United States, 1999–2008. Morbidity and Mortality Weekly Report 59: 1141– 1146. 20829748
  2. [3]U.S. Department of Health and Human Services (2006) The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. 20669524
  3. [4]U.S. Department of Health and Human Services (2010) How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. 21452462
  4. [6]U.S. Department of Health and Human Services (2006) The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General. 20669524
  5. [8]Smith CJ, Perfetti TA, Garg R, Hansch C (2003) IARC carcinogens reported in cigarette mainstream smoke and their calculated log P values. Food Chem Toxicol 41: 807– 817. 12738186
  6. [9]Husgafvel-Pursiainen K (2004) Genotoxicity of environmental tobacco smoke: a review. Mutat Res 567: 427– 445. 15572289
  7. [10]Dizdaroglu M (2012) Oxidatively induced DNA damage: mechanisms, repair and disease. Cancer Lett 327: 26– 47. 22293091
  8. [11]Janik J, Swoboda M, Janowska B, Cieśla JM, Gackowski D, et al (2011) 8-Oxoguanine incision activity is impaired in lung tissues of NSCLC patients with the polymorphism of OGG1 and XRCC1 genes. Mutat Res 709–710: 21– 31. 21376741
  9. [12]Hang B (2006) Base Excision Repair. In: Wei Q, Li L, Chen DJ, editors. DNA Repair, Genetic Instability, and Cancer. Singapore: World Scientific Publishing Co. Pvt.Ltd., pp 23–64.
  10. [13]Zhong DY, Chu HY, Wang ML, Ma L, Shi DN, et al (2012) Meta-analysis demonstrates lack of association of the hOGG1 Ser326Cys polymorphism with bladder cancer risk. Genet Mol Res 11: 3490– 3496. 23079842
  11. [14]Wei W, He XF, Qin JB, Su J, Li SX, et al (2012) Association between the OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk: a meta-analysis. Mol Biol Rep 39: 11249– 11262. 23065211
  12. [15]Lin CH, Chen PM, Cheng YW, Chen CY, Yuan CJ, et al (2012) The APE1 Asp/Asp genotype and the combination of APE1 Asp/Asp and hOGG1-Cys variants are associated with increased p53 mutation in non-small cell lung cancer. J Epidemiol 22: 537– 542. 23038158 PMC3798566
  13. [16]Dey S, Maiti AK, Hegde ML, Hegde PM, Boldogh I, et al (2012) Increased risk of lung cancer associated with a functionally impaired polymorphic variant of the human DNA glycosylase NEIL2. DNA Repair (Amst) 11: 570– 578. 22497777 PMC3361577
  14. [17]Hazra TK, Izumi T, Boldogh I, Imhoff B, Kow YW, et al (2002) Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA. Proc Natl Acad Sci U S A 99: 3523– 3528. 11904416 PMC122556
  15. [18]Hazra TK, Kow YW, Hatahet Z, Imhoff B, Boldogh I, et al (2002) Identification and characterization of a novel human DNA glycosylase for repair of cytosine-derived lesions. J Biol Chem 277: 30417– 30420. 12097317
  16. [19]Bhakat KK, Mokkapati SK, Boldogh I, Hazra TK, Mitra S (2006) Acetylation of human 8-oxoguanine-DNA glycosylase by p300 and its role in 8-oxoguanine repair in vivo. Mol Cell Biol 26: 1654– 1665. 16478987 PMC1430230
  17. [20]Knoll M, Shaoulian R, Magers T, Talbot P (1995) Ciliary beat frequency of hamster oviducts is decreased in vitro by exposure to solutions of mainstream and sidestream cigarette smoke. Biol Reprod 53: 29– 37. 7669854
  18. [21]Knoll M, Talbot P (1998) Cigarette smoke inhibits oocyte cumulus complex pick-up by the oviduct in vitro independent of ciliary beat frequency. Reprod Toxicol 12: 57– 68. 9431573
  19. [23]Jacob P 3rd, Goniewicz ML, Havel C, Schick CF, Benowitz NL (2013) Nicotelline: A Proposed Biomarker and Environmental Tracer for Particulate Matter Derived from Tobacco Smoke. Chem Res Toxicol 26: 1615– 1631. 24125094 PMC3929594
  20. [24]Santos JH, Meyer JN, Mandavilli BS, Van Houten B (2006) Quantitative PCR-based measurement of nuclear and mitochondrial DNA damage and repair in mammalian cells. Methods Mol Biol 314: 183– 199. 16673882
  21. [25]Jung SN, Yang WK, Kim J, Kim HS, Kim EJ, et al (2008) Reactive oxygen species stabilize hypoxia-inducible factor-1 alpha protein and stimulate transcriptional activity via AMP-activated protein kinase in DU145 human prostate. Carcinogenesis 29: 713– 721. 18258605
  22. [26]Roszkowski K, Jozwicki W, Blaszczyk P, Mucha-Malecka A, Siomek A (2011) Oxidative damage DNA: 8-oxoGua and 8-oxodG as molecular markers of cancer. Med Sci Monit 17: CR329– 333. 21629187 PMC3539537
  23. [27]Delaney S, Jarem DA, Volle CB, Yennie CJ (2012) Chemical and biological consequences of oxidatively damaged guanine in DNA. Free Radic Res 46: 420– 441. 22239655 PMC3646368
  24. [28]Izzotti A, Bagnasco M, D'Agostini F, Cartiglia C, Lubet RA, et al (1999) Formation and persistence of nucleotide alterations in rats exposed whole-body to environmental cigarette smoke. Carcinogenesis 20: 1499– 1505. 10426798
  25. [29]Howard DJ, Briggs LA, Pritsos CA (1998) Oxidative DNA damage in mouse heart, liver, and lung tissue due to acute side-stream tobacco smoke exposure. Arch Biochem Biophys 352: 293– 297. 9587419
  26. [30]Matt GE, Quintana PJ, Destaillats H, Gundel LA, Sleiman M (2011) Thirdhand tobacco smoke: emerging evidence and arguments for a multidisciplinary research agenda. Environ Health Perspect 119: 1218– 1226. 21628107 PMC3230406
  27. [31]Pfeifer GP, Denissenko MF, Olivier M, Tretyakova N, Hecht SS, et al (2002) Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene 21: 7435– 7451. 12379884
  28. [32]Feng Z, Hu W, Hu Y, Tang M-S (2006) Acrolein is a major cigarette-related lung cancer agent: preferential binding at p53 mutational hotspots and inhibition of DNA repair. Proc Natl Acad Sci U S A 103: 15404– 15409. 17030796 PMC1592536
  29. [33]Feng Z, Hu W, Chen JX, Pao A, Li H, et al (2006) Preferential DNA damage and poor repair determine ras gene mutational hotspot in human cancer,. J Natl Cancer Inst 94: 1527– 1536. 12381705
  30. [34]Friedberg EC, Walker GC, Siede W, Wood RD, Schultz RA, et al. (2006) DNA repair and mutagenesis. Washington: ASM Press.
  31. [35]Sarker AH, Ikeda S, Nakano H, Terato H, Ide H (1998) Cloning and characterization of a mouse homologue (mNthl1) of Escherichia coli endonuclease III. J Mol Biol 282: 761– 774. 9743625
  32. [36]Dou H, Mitra S, Hazra TK (2003) Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2. J Biol Chem 278: 49679– 49684. 14522990
  33. [37]Zhai X, Zhao H, Liu Z, Wang LE, El-Naggar AK, et al (2008) Functional variants of the NEIL1 and NEIL2 genes and risk and progression of squamous cell carcinoma of the oral cavity and oropharynx. Clin Cancer Res 14: 4345– 4352. 18594018 PMC3025759
  34. [38]Paz-Elizur T, Krupsky M, Blumenstein S, Elinger D, Schechtman E, et al (2003) DNA repair activity for oxidative damage and risk of lung cancer. J Natl Cancer Inst 95: 1312– 1319. 12953085

Cited by

Sorted by citations

Authors
Sarker, A. H., Chatterjee, A., Williams, M., Lin, S., Havel, C., Jacob III, P., Boldogh, I., Hazra, T. K., Talbot, P., & Hang, B.
Affiliations
  • Lawrence Berkeley National Laboratory (US)
  • The University of Texas Medical Branch at Galveston (US)
  • University of California, Riverside (US)
  • San Francisco General Hospital (US)
Corresponding author
  • Sarker, Altaf H.
  • Hang, Bo
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-03-03
Volume
9
Issue
3
Pages
e90261
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0090261
PMC
PMC3945017
OpenAlex
W2010426936
Cited by
44
References
1
Citations by year
2026: 1 · 2025: 3 · 2024: 6 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 4 · 2016: 2 · 2015: 1 · 2014: 3
FWCI
1.37
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
  • U.S. Department of Energy (-AC02-05CH11231, 05CH11231, 19XT-0070, DE AC02 05CH11231, DE-AC02-)
  • Tobacco-Related Disease Research Program (DE-AC02-05CH11231, 20PT-0184, 19XT-0070)
  • Flight Attendant Medical Research Institute
  • National Institutes of Health (DE-AC02–05CH11231, 19XT-0070, CA092584)
  • University of California, San Francisco
  • National Institute on Drug Abuse (P30DA012393)
  • National Cancer Institute (CA-092584, R01CA063503, CA63503, P01CA092584)
  • National Center for Research Resources (S10RR026437)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
Keywords
NEIL2, passive smoking, sidestream smoke, oxidative DNA damage, DNA glycosylase, DNA repair, reactive oxygen species, HIF-1α, lung cancer, lung fibroblasts, BEAS-2B cells, HPRT, POLB, oxidative stress
MeSH terms
Base Sequence, Cell Line, Culture Media, DNA Damage, Humans, Hypoxanthine Phosphoribosyltransferase, Lung, Lung Neoplasms, Smoke, Reactive Oxygen Species, Oxidative Stress, RNA, Small Interfering, DNA-(Apurinic or Apyrimidinic Site) Lyase, DNA Glycosylases, Hypoxia-Inducible Factor 1, alpha Subunit

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review