NEIL2 protects against oxidative DNA damage induced by sidestream smoke in human cells.
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 en...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0090261&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850190216900378624 |
|---|---|
| author | Altaf H Sarker Arpita Chatterjee Monique Williams Sabrina Lin Christopher Havel Peyton Jacob Istvan Boldogh Tapas K Hazra Prudence Talbot Bo Hang |
| author_facet | Altaf H Sarker Arpita Chatterjee Monique Williams Sabrina Lin Christopher Havel Peyton Jacob Istvan Boldogh Tapas K Hazra Prudence Talbot Bo Hang |
| author_sort | Altaf H Sarker |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-35f8818480f9435c8bcd8074ea5d512a |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-35f8818480f9435c8bcd8074ea5d512a2025-08-20T02:15:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9026110.1371/journal.pone.0090261NEIL2 protects against oxidative DNA damage induced by sidestream smoke in human cells.Altaf H SarkerArpita ChatterjeeMonique WilliamsSabrina LinChristopher HavelPeyton JacobIstvan BoldoghTapas K HazraPrudence TalbotBo HangSecondhand 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0090261&type=printable |
| spellingShingle | Altaf H Sarker Arpita Chatterjee Monique Williams Sabrina Lin Christopher Havel Peyton Jacob Istvan Boldogh Tapas K Hazra Prudence Talbot Bo Hang NEIL2 protects against oxidative DNA damage induced by sidestream smoke in human cells. PLoS ONE |
| title | NEIL2 protects against oxidative DNA damage induced by sidestream smoke in human cells. |
| title_full | NEIL2 protects against oxidative DNA damage induced by sidestream smoke in human cells. |
| title_fullStr | NEIL2 protects against oxidative DNA damage induced by sidestream smoke in human cells. |
| title_full_unstemmed | NEIL2 protects against oxidative DNA damage induced by sidestream smoke in human cells. |
| title_short | NEIL2 protects against oxidative DNA damage induced by sidestream smoke in human cells. |
| title_sort | neil2 protects against oxidative dna damage induced by sidestream smoke in human cells |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0090261&type=printable |
| work_keys_str_mv | AT altafhsarker neil2protectsagainstoxidativednadamageinducedbysidestreamsmokeinhumancells AT arpitachatterjee neil2protectsagainstoxidativednadamageinducedbysidestreamsmokeinhumancells AT moniquewilliams neil2protectsagainstoxidativednadamageinducedbysidestreamsmokeinhumancells AT sabrinalin neil2protectsagainstoxidativednadamageinducedbysidestreamsmokeinhumancells AT christopherhavel neil2protectsagainstoxidativednadamageinducedbysidestreamsmokeinhumancells AT peytonjacob neil2protectsagainstoxidativednadamageinducedbysidestreamsmokeinhumancells AT istvanboldogh neil2protectsagainstoxidativednadamageinducedbysidestreamsmokeinhumancells AT tapaskhazra neil2protectsagainstoxidativednadamageinducedbysidestreamsmokeinhumancells AT prudencetalbot neil2protectsagainstoxidativednadamageinducedbysidestreamsmokeinhumancells AT bohang neil2protectsagainstoxidativednadamageinducedbysidestreamsmokeinhumancells |