Nicotine overrides DNA damage-induced G1/S restriction in lung cells.
As an addictive substance, nicotine has been suggested to facilitate pro-survival activities (such as anchorage-independent growth or angiogenesis) and the establishment of drug resistance to anticancer therapy. Tobacco smoking consists of a variety of carcinogens [such as benzopyrene (BP) and nitro...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-04-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3084701?pdf=render |
| _version_ | 1811327541968896000 |
|---|---|
| author | Takashi Nishioka Daisuke Yamamoto Tongbo Zhu Jinjin Guo Sung-Hoon Kim Chang Yan Chen |
| author_facet | Takashi Nishioka Daisuke Yamamoto Tongbo Zhu Jinjin Guo Sung-Hoon Kim Chang Yan Chen |
| author_sort | Takashi Nishioka |
| collection | DOAJ |
| description | As an addictive substance, nicotine has been suggested to facilitate pro-survival activities (such as anchorage-independent growth or angiogenesis) and the establishment of drug resistance to anticancer therapy. Tobacco smoking consists of a variety of carcinogens [such as benzopyrene (BP) and nitrosamine derivatives] that are able to cause DNA double strand breaks. However, the effect of nicotine on DNA damage-induced checkpoint response induced by genotoxins remains unknown. In this study, we investigated the events occurred during G(1) arrest induced by γ-radiation or BP in nicotine-treated murine or human lung epithelial cells. DNA synthesis was rapidly inhibited after exposure to γ-radiation or BP treatment, accompanied with the activation of DNA damage checkpoint. When these cells were co-treated with nicotine, the growth restriction was compromised, manifested by upregulation of cyclin D and A, and attenuation of Chk2 phosphorylation. Knockdown of cyclin D or Chk2 by the siRNAs blocked nicotine-mediated effect on DNA damage checkpoint activation. However, nicotine treatment appeared to play no role in nocodazole-induced mitotic checkpoint activation. Overall, our study presented a novel observation, in which nicotine is able to override DNA damage checkpoint activated by tobacco-related carcinogen BP or γ-irradiation. The results not only indicates the potentially important role of nicotine in facilitating the establishment of genetic instability to promote lung tumorigenesis, but also warrants a dismal prognosis for cancer patients who are smokers, heavily exposed second-hand smokers or nicotine users. |
| first_indexed | 2024-04-13T15:08:39Z |
| format | Article |
| id | doaj.art-35aaf04f6ec74f7f8b891f322e854291 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T15:08:39Z |
| publishDate | 2011-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-35aaf04f6ec74f7f8b891f322e8542912022-12-22T02:42:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-04-0164e1861910.1371/journal.pone.0018619Nicotine overrides DNA damage-induced G1/S restriction in lung cells.Takashi NishiokaDaisuke YamamotoTongbo ZhuJinjin GuoSung-Hoon KimChang Yan ChenAs an addictive substance, nicotine has been suggested to facilitate pro-survival activities (such as anchorage-independent growth or angiogenesis) and the establishment of drug resistance to anticancer therapy. Tobacco smoking consists of a variety of carcinogens [such as benzopyrene (BP) and nitrosamine derivatives] that are able to cause DNA double strand breaks. However, the effect of nicotine on DNA damage-induced checkpoint response induced by genotoxins remains unknown. In this study, we investigated the events occurred during G(1) arrest induced by γ-radiation or BP in nicotine-treated murine or human lung epithelial cells. DNA synthesis was rapidly inhibited after exposure to γ-radiation or BP treatment, accompanied with the activation of DNA damage checkpoint. When these cells were co-treated with nicotine, the growth restriction was compromised, manifested by upregulation of cyclin D and A, and attenuation of Chk2 phosphorylation. Knockdown of cyclin D or Chk2 by the siRNAs blocked nicotine-mediated effect on DNA damage checkpoint activation. However, nicotine treatment appeared to play no role in nocodazole-induced mitotic checkpoint activation. Overall, our study presented a novel observation, in which nicotine is able to override DNA damage checkpoint activated by tobacco-related carcinogen BP or γ-irradiation. The results not only indicates the potentially important role of nicotine in facilitating the establishment of genetic instability to promote lung tumorigenesis, but also warrants a dismal prognosis for cancer patients who are smokers, heavily exposed second-hand smokers or nicotine users.http://europepmc.org/articles/PMC3084701?pdf=render |
| spellingShingle | Takashi Nishioka Daisuke Yamamoto Tongbo Zhu Jinjin Guo Sung-Hoon Kim Chang Yan Chen Nicotine overrides DNA damage-induced G1/S restriction in lung cells. PLoS ONE |
| title | Nicotine overrides DNA damage-induced G1/S restriction in lung cells. |
| title_full | Nicotine overrides DNA damage-induced G1/S restriction in lung cells. |
| title_fullStr | Nicotine overrides DNA damage-induced G1/S restriction in lung cells. |
| title_full_unstemmed | Nicotine overrides DNA damage-induced G1/S restriction in lung cells. |
| title_short | Nicotine overrides DNA damage-induced G1/S restriction in lung cells. |
| title_sort | nicotine overrides dna damage induced g1 s restriction in lung cells |
| url | http://europepmc.org/articles/PMC3084701?pdf=render |
| work_keys_str_mv | AT takashinishioka nicotineoverridesdnadamageinducedg1srestrictioninlungcells AT daisukeyamamoto nicotineoverridesdnadamageinducedg1srestrictioninlungcells AT tongbozhu nicotineoverridesdnadamageinducedg1srestrictioninlungcells AT jinjinguo nicotineoverridesdnadamageinducedg1srestrictioninlungcells AT sunghoonkim nicotineoverridesdnadamageinducedg1srestrictioninlungcells AT changyanchen nicotineoverridesdnadamageinducedg1srestrictioninlungcells |