Cigarette side-stream smoke lung and bladder carcinogenesis: inducing mutagenic acrolein-DNA adducts, inhibiting DNA repair and enhancing anchorage-independent-growth cell transformation

// Hyun-Wook Lee 1, * , Hsiang-Tsui Wang 1, * , Mao-wen Weng 1, * , Chiu Chin 1 , William Huang 2 , Herbert Lepor 2 , Xue-Ru Wu 2 , William N. Rom 3 , Lung-Chi Chen 1 , Moon-shong Tang 1, 3, 4 1 Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA 2 Department of Urology, New York University School of Medicine, New York, NY, USA 3 Department of Medicine, New York University School of Medicine, New York, NY, USA 4 Department of Pathology, New York University School of Medicine, New York, NY, USA * These authors have contributed equally to this work Correspondence to: Moon-shong Tang, e-mail: moon-shong.tang@nyumc.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 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.