Enhanced expression of EGF receptor and low frequency of ras mutations in X-ray-indnced rat thyroid tumours

Radiation is recognized as a carcinogenic factor for the thyroid gland. In this experimental study, oncogene expression was investigated in radiation- induced rat thyroid tumours. Forty 3-month-old Wistar rats re; ceived X-ray -irradiation to the neck region; 40 animals were untreated controls. After 14 months, thyroid tumours had developed in 25 of the 29 irradiated animals still alive; 76% of these tumours were considered malignant. No tumours de veloped in controls. Mutations of codons 12-13 and 59-63 of H-, K- and N-ra s were analysed by PCR-SSCP (single-strand conformation polymorphism analys is) and sequencing of DNA from thyroid tissue. SSCP indicated a ras mutatio n frequency of 8%, but only one K-ras codon 12 (Gly-Cys) mutation was confi rmed by sequencing. Protooncogene expression was analysed by mRNA slot blot hybridization analysis and immunohistochemistry. K-ras mRNA expression and EGF receptor mRNA and protein expression were significantly increased in t he irradiated animals compared with controls, and in tumours versus nontumo ur tissue. This study of radiation-induced rat thyroid tumours demonstrates that ras expression may be subject to changes apart from activating mutati ons. Increased expression of EGF receptor in the tumours parallels the situ ation in human thyroid cancer.