AIRmax and AIRmin mouse lines show a differential lung inflammatory response and differential lung tumor susceptibility after urethane treatment, thus constituting a good genetic model to investigate differences in gene expression profiles related to inflammatory response and lung tumor susceptibility. The transcript profile of ~24,000 known genes was analyzed in normal lung tissue of untreated and urethane-treated AIRmax and AIRmin mice. In lungs of untreated mice, inflammation associated genes involved in pathways such as “leukocyte transendothelial migration”, “cell adhesion” and “tight junctions” were differentially expressed in AIRmax versus AIRmin mice. Moreover, gene expression levels differed significantly in urethane-treated mice even at 21 days after treatment. In AIRmin mice, modulation of expression of genes involved in pathways associated with inflammatory response paralleled the previously observed persistent infiltration of inflammatory cells in the lung of these mice. In conclusion, a specific gene expression profile in normal lung tissue is associated with mouse line susceptibility or resistance to lung tumorigenesis and with different inflammatory response, and urethane treatment causes a long-lasting alteration of the lung gene expression profile that correlates with persistent inflammatory response of AIRmin mice.
Six AIRmax (3 males and 3 females) and six AIRmin (3 males and 3 females) mice were treated with two intraperitoneal injections of 1 mg/g body weight urethane or saline solution (total of 24 AIR mice: 12 AIRmax and 12 AIRmin mice, 6 urethane- and 6 saline-treated respectively) with a 48-h interval and sacrificed 21 days later