HIGH-FREQUENCY AND LOW SPECIFICITY OF RAS GENE-MUTATIONS IN RAT ZYMBALS GLAND TUMORS INDUCED BY 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE

The activating mutations of all three ras genes in rat Zymbal's gland tumors induced by a food mutagen, 2-amino-3-methylimidazo[4,5-f]quinol ine (IQ) were analyzed. DNA fragments of the Ha-ras, Ki-ras and N-ras oncogenes were amplified from formalin-fixed and paraffin-embedded tis sues by the polymerase chain reaction (PCR) and analyzed for activatin g mutations involving codons 12, 13 and 61 by oligonucleotide differen tial hybridization. All nine Zymbal's gland tumors examined, including three papillomas, were found to contain either an Ha-ras or Ki-ras mu tation. These mutations were located in either codon 13 or 61 of Ha-ra s, and in either codon 12 or 13 of Ki-ras. Of the nine mutations, thre e were G --> T, three were G --> C, two were G --> A and one was A --> T. Of the nine mutations, eight occurred at guanine bases and seven w ere transversions. There was no correlation between the types of mutat ions and the histological types of the tumors. These results suggest t hat ras gene activation is an important early event in the tumorigenes is induced by IQ in rat Zymbal's gland and that mutations at guanine b ases are frequent, though the locations and types of the mutations are not highly specific.