K-ras mutations are frequent in pulmonary squamous cell carcinomas but not in adenocarcinomas of WBN/Kob rats induced by N-nitrosobis(2-oxopropyl)amine.

Pulmonary carcinomas induced by N-nitrosobis(2-oxopropyl) amine (BOP) in WBN/Kob rats were screened for point mutations in the K-ras protooncogene. Exons 1 and 2 were polymerase chain reaction amplified from paraffin-embedded sections, followed by direct DNA sequencing. G --> A transition mutations in the second base of codon 12 of the K-ras gene were found in 6/24 (25%) rat lung tumors induced by BOP. The incidence of point mutations was significantly higher (P < 0.005) in squamous cell carcinomas (5/7; 71%) than in adenocarcinomas (1/17; 6%), suggesting that the mutational activation of K-ras is associated with a differential growth advantage in these two histologically distinct types of lung tumors in rats. No mutations were found in codons 13, 61 or adjacent regions of these codons.