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Mutation of ras oncogene in di-isopropanolnitrosamine-induced rat thyroid carcinogenesis
Yoshihiko Kobayashi1, Akira Kawaoi, Ryohei Katoh
1Fuji Biomedix Co., Ltd. Kobuchizawa Laboratories 10221, Kobuchizawa-cho, Kitakoma-gun, Yamanashi-ken, 408-0044, Japan.
Abstract:
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.
Insights
K-ras gene mutations are frequent in rat thyroid nodules induced by di-isopropanolnitrosamine (DIPN). This ras gene mutation appears to be an early event in thyroid tumorigenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Thyroid tumorigenesis involves complex genetic alterations.
- The role of ras gene mutations in chemically induced thyroid tumors requires further elucidation.
Purpose of the Study:
- To investigate the incidence and role of K-ras gene mutations in rat thyroid lesions induced by di-isopropanolnitrosamine (DIPN).
Main Methods:
- DNA extraction from rat thyroid lesions.
- Microdissection-Polymerase Chain Reaction-Direct Sequencing (MD-PCR-DS) for mutation analysis.
Main Results:
- K-ras gene mutation (G-A transition at codon 12) was detected in 75% of nodular lesions.
- Mutations were absent in diffuse hyperplastic and pre-nodular lesions.
- Mutation incidence correlated with DIPN administration method (serial vs. single injection).
Conclusions:
- K-ras mutation is a significant factor in DIPN-induced rat thyroid tumorigenesis.
- K-ras mutation may represent an early event in this process.