Mutation of ras oncogene in di-isopropanolnitrosamine-induced rat thyroid carcinogenesis

To clarify the role of ras gene mutation in thyroid tumorigenesis, DNAs extracted from various rat thyroid lesions induced by di-isopropanolnitrosamine (DIPN) administration were analyzed using the microdissection–polymerase chain reaction–direct sequence (MD-PCR-DS) method. The MD-PCR-DS method revealed that K-ras gene mutation (G–A transition at codon 12) was frequently detected in nodular lesions (incidence of mutation 75%) and absent in diffuse hyperplastic and pre-nodular lesions. Although the incidence of mutation in nodular lesions was not correlated with the histological type (type 2A 76%; type 2B 84%; and type 3 71%) or treatment period (15 weeks 84% and 30 weeks 71%), it was correlated with the administration method (single injection 55% and serial injection 91%). In conclusion, K-ras mutation plays an important role in DIPN-induced rat thyroid tumorigenesis, possibly regarded as an early event in the tumorigenic process.