We are currently evaluating the role of oncogene activation in the development of chemically induced tumors in nonhuman primates. Oncogene activation has been identified in a wide range of human neoplasms. In rodents, the ras family of oncogenes are activated by single point mutations which result from the interaction of DNA with certain chemical carcinogens. DNA from tumor tissues collected over a period of 25 years from nonhuman primates on long-term treatment with a variety of chemical carcinogens is being examined for the presence of activating point mutations in the N, K and H-ras loci. Using the polymerase chain reaction (PCR), small quantities of DNA obtained from thin sections of paraffin embedded tissue are amplified at the N, K or H-ras loci and their nucleotide sequence obtained following subcloning. However, given the relatively long time period required for subcloning and sequence analysis of each tissue, we are currently developing new techniques for detecting ras mutations in order to expedite the screening of DNA from monkey tissues.
