GENETIC INSTABILITY ASSESSED BY SISTER-CHROMATID EXCHANGE ANALYSIS INTHE DUNNING R-3327 RAT PROSTATIC ADENOCARCINOMA MODEL AND ITS RELATIONSHIP TO METASTATIC POTENTIAL

The original Dunning R-3327 tumor, described in 1962, has given rise t o distinct sublines of different metastatic potentials. The different phenotypes cannot be explained by differences in chromosomal number, D NA content, or nuclear pleomorphism. Sister chromatid exchange is an i nterchange between two strands of DNA indicative of DNA damage. The fr equency of sister chromatid exchanges is a well-accepted measure of ge netic instability. To determine whether an assay of genetic instabilit y could distinguish sublines capable of generating cells of the metast atic phenotype, cells from three sublines of low (<10%) metastatic pot ential and three sublines of high (>90%) metastatic potential were cul tured in 10 mu M 5-bromodeoxyuridine to label DNA. Chromosome preparat ions were made and sister chromatids were differentiated with Hoechst 33258 dye and Giemsa stain. Sixty metaphase spreads from each subline were scored for SCE and chromosome number. The low metastatic sublines G, AT-1, and AT-2 had 0.32 +/- standard deviation 0.10, 0.38 +/- 0.12 , and 0.14 +/- 0.05 sister chromatid exchanges per chromosome, respect ively. The high metastatic sublines AT-3, MAT-Lu, and MAT-LyLu had 0.5 5 +/- 0.17, 0.32 +/- 0.1, and 0.33 +/- 0.2 sister chromatid exchanges per chromosome, respectively. Subline differences in metastatic potent ials cannot be explained by incidences of sister chromatid exchanges. (C) 1995 Wiley-Liss, Inc.