Nicotine does not enhance tumorigenesis in mutant K-Ras-driven mouse models of lung cancer

Colleen R. Maier, M. Christine Hollander, Evthokia A. Hobbs, Irem Dogan, R. Ilona Linnoila, Phillip A. Dennis

Research output: Contribution to journalArticle

Abstract

Smoking is the leading cause of preventable cancer deaths in the United States. Nicotine replacement therapies (NRT) have been developed to aid in smoking cessation, which decreases lung cancer incidence. However, the safety of NRT is controversial because numerous preclinical studies have shown that nicotine enhances tumor cell growth in vitro and in vivo. We modeled NRT in mice to determine the effects of physiologic levels of nicotine on lung tumor formation, tumor growth, or metastasis. Nicotine administered in drinking water did not enhance lung tumorigenesis after treatment with the tobacco carcinogen, 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Tumors that develop in this model have mutations in K-ras, which is commonly observed in smoking-related, human lung adenocarcinomas. In a transgenic model of mutant K-ras-driven lung cancer, nicotine did not increase tumor number or size and did not affect overall survival. Likewise, in a syngeneic model using lung cancer cell lines derived from NNK-treated mice, oral nicotine did not enhance tumor growth or metastasis. These data show that nicotine does not enhance lung tumorigenesis when given to achieve levels comparable with those of NRT, suggesting that nicotine has a dose threshold, below which it has no appreciable effect. These studies are consistent with epidemiologic data showing that NRT does not enhance lung cancer risk in former smokers.

Original languageEnglish (US)
Pages (from-to)1743-1751
Number of pages9
JournalCancer Prevention Research
Volume4
Issue number11
DOIs
StatePublished - Nov 2011
Externally publishedYes

Fingerprint

Nicotine
Lung Neoplasms
Carcinogenesis
Neoplasms
Lung
Growth
Smoking
Neoplasm Metastasis
Therapeutics
Smoking Cessation
Drinking Water
Carcinogens
Tobacco
Safety
Cell Line
Mutation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Maier, C. R., Hollander, M. C., Hobbs, E. A., Dogan, I., Linnoila, R. I., & Dennis, P. A. (2011). Nicotine does not enhance tumorigenesis in mutant K-Ras-driven mouse models of lung cancer. Cancer Prevention Research, 4(11), 1743-1751. https://doi.org/10.1158/1940-6207.CAPR-11-0365

Nicotine does not enhance tumorigenesis in mutant K-Ras-driven mouse models of lung cancer. / Maier, Colleen R.; Hollander, M. Christine; Hobbs, Evthokia A.; Dogan, Irem; Linnoila, R. Ilona; Dennis, Phillip A.

In: Cancer Prevention Research, Vol. 4, No. 11, 11.2011, p. 1743-1751.

Research output: Contribution to journalArticle

Maier, CR, Hollander, MC, Hobbs, EA, Dogan, I, Linnoila, RI & Dennis, PA 2011, 'Nicotine does not enhance tumorigenesis in mutant K-Ras-driven mouse models of lung cancer', Cancer Prevention Research, vol. 4, no. 11, pp. 1743-1751. https://doi.org/10.1158/1940-6207.CAPR-11-0365
Maier, Colleen R. ; Hollander, M. Christine ; Hobbs, Evthokia A. ; Dogan, Irem ; Linnoila, R. Ilona ; Dennis, Phillip A. / Nicotine does not enhance tumorigenesis in mutant K-Ras-driven mouse models of lung cancer. In: Cancer Prevention Research. 2011 ; Vol. 4, No. 11. pp. 1743-1751.
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