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K-ras activation by point mutation in codon 12 has been reported in lung adenocarcinomas in various models of experimental lung tumours induced by chemical carcinogens. The hypothesis of the presence of cells containing K-ras mutation in non neoplastic bronchial carina, the main site of impaction of airborne contaminants, was investigated by evaluating concurrent lung tumour and non-neoplastic proximal bronchial carinae from 19 patients with lung adenocarcinomas. The restriction fragment length polymorphism enriched PCR method used can detect one mutant allele among 10(3) normal alleles. A mutation was detected in 42% of lung adenocarcinoma samples. No mutation was detected in either tumour or bronchial carinae in nine patients (47%). K-ras mutation was detected in the lung tumour but not in bronchial carinae in four patients (21%), in both the lung tumour and bronchial carinae in four other patients (21%). In two patients (11%), K-ras mutation was detected in at least one bronchial carina, but not in the lung tumour. Mutations of codon 12, confirmed by sequencing analysis of ten samples, were G to T transversion, mostly TGT and GTT in bronchial carinae and lung tumours. Our data show that activated K-ras by point mutation can be present in non-neoplastic bronchial carina mucosa even when no mutation is detected in tumour samples.

Detection of codon 12 K- ras mutations in non-neoplastic mucosa from bronchial carina in patients with lung adenocarcinomas