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Oncotarget. 2015 Oct 20;6(32):33226-36. doi: 10.18632/oncotarget.5429.

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

Author information

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.

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.

KEYWORDS:

DNA damage and repair; acrolein and BPDE; anchorage independent growth; lung and bladder cancer; second-hand and side-stream smoke

PMID:
26431382
PMCID:
PMC4741761
DOI:
10.18632/oncotarget.5429
[Indexed for MEDLINE]
Free PMC Article

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