Induction of Lung Tumors and Mutational Analysis in FVB/N Mice Treated with the Tobacco Carcinogen 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone

Methods Mol Biol. 2020:2102:149-160. doi: 10.1007/978-1-0716-0223-2_7.

Abstract

Lung cancer remains the leading cause of cancer-related deaths worldwide. In order to understand lung cancer biology and evaluate novel therapeutic strategies, preclinical mouse models have been developed that mimic early and advanced-stage lung cancer. Among autochthonous models, carcinogen-induced systems are valuable preclinical tools since tobacco smoking remains the number one risk factor for lung tumor development. Among the several thousand chemicals within cigarette smoke, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent carcinogen with tumorigenic effects described in both mice and humans. Herein, we describe the methodology for inducing lung tumors in mice using the tobacco carcinogen NNK and subsequent lung fixation for quantitative assessment of tumor development and analysis of oncogenic mutations in tumors.

Keywords: Lung cancer; Lung fixation; Lung histology; Murine model; Tobacco carcinogen.

MeSH terms

  • Animals
  • Carcinogens / toxicity*
  • DNA / genetics
  • DNA / isolation & purification
  • DNA Mutational Analysis
  • Disease Models, Animal*
  • Immunohistochemistry
  • Lung / cytology
  • Lung / pathology*
  • Lung / surgery*
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Mice
  • Mice, Inbred Strains
  • Nicotiana / toxicity
  • Nitrosamines / administration & dosage
  • Nitrosamines / toxicity*
  • Workflow

Substances

  • Carcinogens
  • Nitrosamines
  • 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
  • DNA