Neutrophils are required for 3-methylcholanthrene-initiated, butylated hydroxytoluene-promoted lung carcinogenesis

Mol Carcinog. 2012 Dec;51(12):993-1002. doi: 10.1002/mc.20870. Epub 2011 Oct 17.


Multiple studies have shown a link between chronic inflammation and lung tumorigenesis. Inbred mouse strains vary in their susceptibility to methylcholanthrene (MCA)-initiated butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated whether neutrophils play a role in strain dependent differences in susceptibility to lung tumor promotion. We observed a significant elevation in homeostatic levels of neutrophils in the lungs of tumor-susceptible BALB/cByJ (BALB) mice compared to tumor-resistant C57BL/6J (B6) mice. Additionally, BHT treatment further elevated neutrophil numbers as well as neutrophil chemoattractant keratinocyte-derived cytokine (KC)/chemokine (C-X-C motif) ligand 1 (Cxcl1) levels in BALB lung airways. Lung CD11c+ cells were a major source of KC expression and depletion of neutrophils in BALB mice resulted in a 71% decrease in tumor multiplicity. However, tumor multiplicity did not depend on the presence of T cells, despite the accumulation of T cells following BHT treatment. These data demonstrate that neutrophils are essential to promote tumor growth in the MCA/BHT two-step lung carcinogenesis model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butylated Hydroxytoluene / toxicity*
  • Carcinogens / toxicity*
  • Cell Transformation, Neoplastic
  • Female
  • Flow Cytometry
  • Immunologic Memory
  • Immunophenotyping
  • Lung Neoplasms / chemically induced*
  • Lung Neoplasms / immunology*
  • Methylcholanthrene / toxicity*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neutrophils / immunology*
  • T-Lymphocytes / immunology


  • Carcinogens
  • Butylated Hydroxytoluene
  • Methylcholanthrene