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,Xue-Ru Wu,Mao-Wen Weng,William Huang,William N Rom,Herbert Lepor,Hsiang-Tsui Wang,Chiu Chin,Moon-Shong Tang,Lung-Chi Chen

doi:10.18632/oncotarget.5429

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.

Highlights

Cigarette smoke (CS) is the major cause of human cancer, with more than 5 million CS-related cancer deaths worldwide annually [1]
Tobacco smoke is the major cause of human cancer; this conclusion is mainly derived from smokers have a higher cancer incidence than the general population, that main stream smoke contains a variety of human carcinogens, and that mainstream smoke (MSS) causes cancer in animal models [26, 57,58,59,60]
The current study presents evidence that side-stream smoke (SSS) induces mutagenic Acr-dG adducts, inhibits DNA repair, and causes degradation of DNA repair proteins

Summary

Introduction

Cigarette smoke (CS) is the major cause of human cancer, with more than 5 million CS-related cancer deaths worldwide annually [1]. Acr enhances the susceptibility of cells to mutagenesis [18, 20, 21] These findings raise the possibility that induction of DNA damage by PAHs and Acr and inhibition of DNA repair by Acr are two mechanisms by which SSS causes toxic, mutagenic, and perhaps tumorigenic effects. We tested this possibility by determining the levels of two major classes of DNA adduct induced by PAHs and aldehydes: benzo(a) pyrene diol epoxide (BPDE)-DNA adducts and aldehydeinduced cyclic propano-deoxyguanosine (PdG) adducts in bronchoalveolar lavage (BAL), lung, heart, liver, and bladder-mucosa tissues from mice exposed to SSS for 8 and 16 weeks. We propose that these are the three mechanisms by which SHS causes lung and bladder cancers

Methods

Results

Conclusion