Abstract
To investigate the modifying effects of repeated doses of NNK on the development of lung tumors in hamsters with pulmonary fibrosis, female Syrian golden hamsters received 5 subcutaneous (s.c.) injections of 0.6 mg MNUR (Groups I and II) or 0.5% ethanol solution (Groups III and IV), at 2-week intervals, and were then given distilled water containing 3 ppm NNK (Groups I and III) or water alone (Groups II and IV) for 27 weeks. Glandular metaplasia, papillary hyperplasia and bronchiolo-alveolar adenomas were induced in the lungs of all the animals of Groups I and II without any significant differences in data for multiplicity and PCNA labeling indices of these between Groups I and II. In PCR-dot blod hybridization analysis on lung proliferative lesions, point mutations of c-K-ras gene at codon 12 or 61 were seen in bronchiolo-alveolar adenomas and carcinomas from animals of Group I. The mutation incidences were 4/13 in adenomas and 3/4 in carcinomas, involving changes from GGT-to GAT at codon 12, or CAA-to-CGA at codon 61. The results indicate that NNK treatment with the present dose regimen exerts no modifying effects on the development of lung proliferative lesions in hamsters with pulmonary fibrosis induced by MNUR.
