Lung cancer is one of the deadliest types of
cancer and as such requires disease models that are useful for identification of novel pathways for
biomarkers as well as to test therapeutic agents.
Adenocarcinoma (ADC), the most prevalent type of
lung cancer, is a subtype of
non-small cell lung carcinoma (NSCLC) and a disease driven mainly by smoking. However, it is also the most common subtype of
lung cancer found in non-smokers with environmental exposures. Chemically driven models of
lung cancer, also called primary models of
lung cancer, are important because they do not overexpress or delete oncogenes or tumor suppressor genes, respectively, to increase
oncogenesis. Instead these models test
tumor development without forcing a specific pathway (i.e., Kras). The primary focus of this chapter is to discuss a well-established 2-stage mouse model of
lung adenocarcinomas. The initiator (3-methylcholanthrene, MCA) does not elicit many, if any,
tumors if not followed by exposure to the
tumor promoter (
butylated hydroxytoluene,
BHT). In sensitive strains, such as A/J, FVB, and BALB, significantly greater numbers of
tumors develop following the MCA/
BHT protocol compared to MCA alone.
BHT does not elicit
tumors on its own; it is a non-genotoxic
carcinogen and promoter. In these sensitive strains, promotion is also associated with
inflammation characterized by infiltrating macrophages, lymphocytes, and neutrophils, and other inflammatory cell types in addition to increases in total
protein content reflective of lung hyperpermeability. This 2-stage model is a useful tool to identify unique promotion specific events to then test in future intervention studies.