Genetic instability assessed by sister chromatid exchange analysis in the Dunning R-3327 rat prostatic adenocarcinoma model and its relationship to metastatic potential.
The original Dunning R-3327 tumor, described in 1961, has given rise to distinct sublines of different metastatic potentials. The different phenotypes cannot be explained by differences in chromosomal number, DNA content, or nuclear pleomorphism. Sister chromatid exchange is an interchange between two strands of DNA indicative of DNA damage. The frequency of sister chromatid exchanges is a well-accepted measure of genetic instability. To determine whether an assay of genetic instability could distinguish sublines capable of generating cells of the metastatic phenotype, cells from three sublines of low (< 10%) metastatic potential and three sublines of high (> 90%) metastatic potential were cultured in 10 microM 5-bromodeoxyuridine to label DNA. Chromosome preparations 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, respectively. The high metastatic sublines AT-3, MAT-Lu, and MAT-LyLu had 0.55 +/- 0.17, 0.32 +/- 0.1, and 0.33 +/- 0.2 sister chromatid exchanges per chromosome, respectively. Subline differences in metastatic potentials cannot be explained by incidences of sister chromatid exchanges.
Sharief
Y
Y
Department of Surgery, University of North Carolina at Chapel Hill, USA.
Mohler
J L
JL
D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary*; D000818:Animals; D002875:Chromosomes; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D051381:Rats; D012854:Sister Chromatid Exchange; D014407:Tumor Cells, Cultured