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Chronic cigarette smoke extract treatment selects for apoptotic dysfunction and mitochondrial mutations in minimally transformed oral keratinocytes.

Publication ,  Journal Article
Chang, SS; Jiang, WW; Smith, I; Glazer, C; Sun, W-Y; Mithani, S; Califano, JA
Published in: Int J Cancer
January 1, 2010

Cigarette smoke demonstrates a carcinogenic effect through chronic exposure, not acute exposures. However, current cell line models study only the acute effects of cigarette smoke. Using a cell line model, we compared the effects of acute versus chronic cigarette smoke extract (CSE) on mitochondria in minimally transformed oral keratinocytes (OKF6). OKF6 cells were treated with varying concentrations of CSE for 6 months. Cells were analyzed monthly by flow cytometry for mitochondrial membrane potential (MMP), cytochrome c release, caspase 3 activation and viability after CSE exposure. At each time point, the same assays were performed after 24 hr of valinomycin (MMP-depolarizing agent) treatment. The mitochondrial DNA of chronically CSE-treated cells was sequenced. After 6 months of CSE treatment, the cells were increasingly resistant to CSE-mediated and valinomycin-induced cell death. In addition, chronic CSE treatment caused chronic depolarization of MMP, cytochrome c release and caspase activation. Cells grown in the presence of only CSE vapor also exhibited the same resistance and chronic baseline apoptotic activation. Mitochondrial DNA sequencing found that chronic CSE-treated cells had more amino acid-changing mitochondrial mutations than acutely treated cells. CSE treatment of normal cells select for apoptotic dysfunction as well as mitochondrial mutations. These findings suggest that chronic tobacco exposure induces carcinogenesis via selection of apoptosis resistance and mitochondrial mutation in addition to previously known genotoxic effects that were found by acute treatments. Chronic models of tobacco exposure on upper aerodigestive epithelia may be more insightful than models of acute exposure in studying head and neck carcinogenesis.

Duke Scholars

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

January 1, 2010

Volume

126

Issue

1

Start / End Page

19 / 27

Location

United States

Related Subject Headings

  • Valinomycin
  • Smoke
  • Oncology & Carcinogenesis
  • Nicotiana
  • Mutation
  • Membrane Potentials
  • Keratinocytes
  • Humans
  • Flow Cytometry
  • Enzyme Activation
 

Citation

APA
Chicago
ICMJE
MLA
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Chang, S. S., Jiang, W. W., Smith, I., Glazer, C., Sun, W.-Y., Mithani, S., & Califano, J. A. (2010). Chronic cigarette smoke extract treatment selects for apoptotic dysfunction and mitochondrial mutations in minimally transformed oral keratinocytes. Int J Cancer, 126(1), 19–27. https://doi.org/10.1002/ijc.24777
Chang, Steven S., Wei Wen Jiang, Ian Smith, Chad Glazer, Wen-Yue Sun, Suhail Mithani, and Joseph A. Califano. “Chronic cigarette smoke extract treatment selects for apoptotic dysfunction and mitochondrial mutations in minimally transformed oral keratinocytes.Int J Cancer 126, no. 1 (January 1, 2010): 19–27. https://doi.org/10.1002/ijc.24777.
Chang SS, Jiang WW, Smith I, Glazer C, Sun W-Y, Mithani S, et al. Chronic cigarette smoke extract treatment selects for apoptotic dysfunction and mitochondrial mutations in minimally transformed oral keratinocytes. Int J Cancer. 2010 Jan 1;126(1):19–27.
Chang, Steven S., et al. “Chronic cigarette smoke extract treatment selects for apoptotic dysfunction and mitochondrial mutations in minimally transformed oral keratinocytes.Int J Cancer, vol. 126, no. 1, Jan. 2010, pp. 19–27. Pubmed, doi:10.1002/ijc.24777.
Chang SS, Jiang WW, Smith I, Glazer C, Sun W-Y, Mithani S, Califano JA. Chronic cigarette smoke extract treatment selects for apoptotic dysfunction and mitochondrial mutations in minimally transformed oral keratinocytes. Int J Cancer. 2010 Jan 1;126(1):19–27.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

January 1, 2010

Volume

126

Issue

1

Start / End Page

19 / 27

Location

United States

Related Subject Headings

  • Valinomycin
  • Smoke
  • Oncology & Carcinogenesis
  • Nicotiana
  • Mutation
  • Membrane Potentials
  • Keratinocytes
  • Humans
  • Flow Cytometry
  • Enzyme Activation