MICROSATELLITE INSTABILITY IN AN ANIMAL-MODEL OF MAMMARY CARCINOGENESIS

Alterations in the length of simple repetitive genomic sequences (micr osatellite instability, MSI) may characterize a distinct mechanism of mammary carcinogenesis. In order to investigate whether MSI is associa ted with chemically-induced mammary carcinogenesis in the rat, 30 micr odissected mammary carcinomas were analyzed using 27 different microsa tellite markers from chromosomes 1, 3, 5, 7 and 8. DNA was extracted f rom rat mammary cancer and adjoining microscopically normal tissues fr om the same slide, amplified by PCR, using different polymorphic DNA m arkers and the reaction products were analyzed for microsatellite inst ability. The results of this study indicate that 30% of cases (9 out o f 30) showed microsatellite instability at a minimum of 1 locus. Three cases (out of 30) showed microsatellite instability at only three loc i or less, called MSI-L (low frequency MSI). Six cases (out of 30) sho wed MSI at four loci or more, called MSI-H (high frequency MSI). Six c ases showed MSI at D5Mit11 and D5Mgh3 loci, five cases showed MSI at D 1Mit14 D1Mgh6, D5Mgh5 and D8Mgh10 loci, four cases had MSI at D1Mgh2, and D3Mgh7 loci, three cases had MSI at D3Mit3, D3Mgh5, D7Mgh1 loci, t wo cases had MSI at D7Mit11 locus and one case had MSI at D3Mgh9 locus . The results of these experiments suggest that MSI may be an importan t etiological event in the pathophysiology of mammary carcinogenesis.