Cigarette side-stream smoke lung and bladder carcinogenesis: inducing mutagenic acrolein-DNA adducts, inhibiting DNA repair and enhancing anchorage-independent-growth cell transformation
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Hyun-Wook Lee1,*, Hsiang-Tsui Wang1,*, Mao-wen Weng1,*, Chiu Chin1, William Huang2, Herbert Lepor2, Xue-Ru Wu2, William N. Rom3, Lung-Chi Chen1, Moon-shong Tang1,3,4
1Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA
2Department of Urology, New York University School of Medicine, New York, NY, USA
3Department of Medicine, New York University School of Medicine, New York, NY, USA
4Department of Pathology, New York University School of Medicine, New York, NY, USA
*These authors have contributed equally to this work
Moon-shong Tang, e-mail: firstname.lastname@example.org
Keywords: second-hand and side-stream smoke, acrolein and BPDE, DNA damage and repair, lung and bladder cancer, anchorage independent growth
Received: July 09, 2015 Accepted: September 16, 2015 Published: September 28, 2015
Second-hand smoke (SHS) is associated with 20–30% of cigarette-smoke related diseases, including cancer. Majority of SHS (>80%) originates from side-stream smoke (SSS). Compared to mainstream smoke, SSS contains more tumorigenic polycyclic aromatic hydrocarbons and acrolein (Acr). We assessed SSS-induced benzo(a)pyrene diol epoxide (BPDE)- and cyclic propano-deoxyguanosine (PdG) adducts in bronchoalveolar lavage (BAL), lung, heart, liver, and bladder-mucosa from mice exposed to SSS for 16 weeks. In SSS exposed mice, Acr-dG adducts were the major type of PdG adducts formed in BAL (p < 0.001), lung (p < 0.05), and bladder mucosa (p < 0.001), with no significant accumulation of Acr-dG adducts in heart or liver. SSS exposure did not enhance BPDE-DNA adduct formation in any of these tissues. SSS exposure reduced nucleotide excision repair (p < 0.01) and base excision repair (p < 0.001) in lung tissue. The levels of DNA repair proteins, XPC and hOGG1, in lung tissues of exposed mice were significantly (p < 0.001 and p < 0.05) lower than the levels in lung tissues of control mice. We found that Acr can transform human bronchial epithelial and urothelial cells in vitro. We propose that induction of mutagenic Acr-DNA adducts, inhibition of DNA repair, and induction of cell transformation are three mechanisms by which SHS induces lung and bladder cancers.
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