Fig. 4. DNA damage analysis in lung tissues from 2-months old mice with different genetic alterations.

A: Fresh lung tissues from the control, Xpc^−/−, Kras^LA1 and Xpc^−/−Kras^LA1 mice were processed to measure DNA damage using the COMET assay. Bronchial epithelial cells were isolated and subjected to COMET assay. For each sample, 200 independent cells were evaluated. The difference between the control mice and the other three groups (Xpc^−/−, Kras^LA1 or Xpc^−/−Kras^LA1) were significant (with a P value <0.05; as indicated by *). Data from the Xpc^−/−Kras^LA1 mice were significantly higher than mice with a single gene mutation (Xpc^−/−or Kras^LA1) (with a P value < 0.05, indicated by **) or the sum from two single mutant mice. According to BLISS independence analysis, Xpc loss and Kras^LA1 expression had a more than additive effect (synergy) on induction of DNA damage.