Title: Cigarette side-stream smoke lung and bladder carcinogenesis: inducing mutagenic acrolein-DNA adducts, inhibiting DNA repair and enhancing anchorage-independent-growth cell transformation.
Authors: Lee, Hyun-Wook; Wang, Hsiang-Tsui; Weng, Mao-wen; Chin, Chiu; Huang, William; Lepor, Herbert; Wu, Xue-Ru; Rom, William N; Chen, Lung-Chi; Tang, Moon-shong
Published In Oncotarget, (2015 Oct 20)
Abstract: 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.
PubMed ID: 26431382
MeSH Terms: Acrolein/adverse effects; Acrolein/metabolism*; Animals; Carcinogenesis/genetics*; Carcinogenesis/pathology; Cell Adhesion/drug effects; Cell Proliferation/drug effects; Cell Transformation, Neoplastic/drug effects; Cell Transformation, Neoplastic/metabolism; DNA Adducts/adverse effects; DNA Adducts/metabolism*; DNA Repair/drug effects*; Lung Neoplasms/etiology; Lung Neoplasms/genetics*; Lung Neoplasms/pathology; Male; Mice; Smoke/adverse effects*; Tobacco Products/adverse effects*; Urinary Bladder Neoplasms/genetics*; Urinary Bladder Neoplasms/pathology