Absence of the c-Ha-ras and c-Ki-ras oncogene mutations in the hermaphroditic fish Rivulus marmoratus papillary thyroid carcinomas induced by N-methyl-N′-nitro-N-nitrosoguanidine

Previously we reported that papillary thyroid carcinomas were predominantly induced at high frequency by a low dose of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) in the hermaphroditic fish Rivulus marmoratus. In the current study, polymerase chain reaction (PCR) amplification and direct sequencing were used to examine the point mutations of Ha- and Ki-ras genes, which may be associated with papillary thyroid tumour development in rivulus. Thirty-three tumour samples were tested, however, no mutations were detected in rivulus Ha- and Ki-ras genes. In human and rodent models, it has been reported that ras gene mutations in papillary thyroid tumours occurred preferentially in the N-ras gene in general, while follicular tumours contained activated Ha- or Ki-ras gene mutations. This may explain why papillary thyroid carcinomas in rivulus were not mutated at codon 12, 13 or 61 of exon 1 or exon 2 of the rivulus Ha- or Ki-ras gene. These results imply that another oncogene, such as the N-ras gene and others, may be preferentially activated in rivulus papillary thyroid carcinomas, and also give valuable information for comparative studies of papillary thyroid carcinogenesis.