The activation of K-ras gene at an early stage of lung tumorigenesis in mice.

To clarify the exact timing of K-ras gene mutational activation in lung tumorigenesis of mice, we applied a sensitive mutant allele specific amplification (MASA) method to pulmonary DNA from urethane-treated mice. The activation of K-ras gene with 61st codon AT mutation was detected in the lungs of mice at day 14 but not day 7 after urethane treatment by MASA. The mutation of MASA products was also checked by XbaI restriction fragment length polymorphism analysis and DNA sequencing. These data suggest that the mutation of K-ras gene in the lungs of mice treated with urethane occurred at the early stage of lung tumorigenesis.