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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Maier, CR; Hollander, MC; Hobbs, EA; Dogan, I; Linnoila, RI; Dennis, PA

Published Date

  • November 2011

Published In

Volume / Issue

  • 4 / 11

Start / End Page

  • 1743 - 1751

PubMed ID

  • 22027685

Pubmed Central ID

  • PMC3208746

Electronic International Standard Serial Number (EISSN)

  • 1940-6215

Digital Object Identifier (DOI)

  • 10.1158/1940-6207.CAPR-11-0365


  • eng

Conference Location

  • United States