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.
Ohgaki
H
H
Department of Pathology, University of Zürich, Switzerland.
Furukawa
F
F
Takahashi
M
M
Kleihues
P
P
D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics*; D004277:DNA, Single-Stranded; D011905:Genes, ras; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009602:Nitrosamines / Q000633:toxicity*; D017354:Point Mutation; D051381:Rats
D004277:DNA, Single-Stranded; D009602:Nitrosamines; C013622:nitrosobis(2-oxopropyl)amine; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone