Fluorescence in situ hybridisation with chromosome-specific centromeric probes: a sensitive method to detect aneuploidy.
Cytochalasin B-blocked binucleate human lymphocytes from female donors have been used to measure micronucleus induction and other aneuploidy events after treatment with colchicine, vinblastine or carbendazim. For the aneuploidy events, centromeric probes for 6 selected chromosomes (1, 8, X, 11, 17, 18) were used to measure chromosome loss, addition and non-disjunction in the interphase nuclei of these binucleate cells. The chromosomes were probed in pairs using Cy-3 (red) and FITC (green) labels for the 2 different centromeric regions. For colchicine, the total non-disjunction frequencies for chromosomes 1 and 8 were similar to the total micronucleus frequencies, but were detected as significant at lower concentrations. For vinblastine (chromosomes 1 and 8) and carbendazim (all 6 chromosomes) the frequencies of non-disjunction far exceeded (7 and > 2-fold, respectively) the peak frequencies of micronucleus induction. Although most chromosomes exhibited similar sensitivity in all the aneuploidy events measured, there was an indication that chromosome X was more than susceptible to non-disjunction than the other chromosomes. We believe that measurement of non-disjunction in binucleate human lymphocytes using chromosome specific centromeric probes offers a sensitive method for detection of aneuploidy and is particularly appropriate for the establishment of thresholds.
Marshall
R R
RR
Corning Hazleton Europe, Harrogate, UK.
Murphy
M
M
Kirkland
D J
DJ
Bentley
K S
KS
D000328:Adult; D000782:Aneuploidy; D001562:Benzimidazoles / Q000494:pharmacology; D002219:Carbamates; D002478:Cells, Cultured; D002503:Centromere; D003078:Colchicine / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D015342:DNA Probes; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007399:Interphase; D008214:Lymphocytes; D015162:Micronucleus Tests; D009630:Nondisjunction, Genetic; D011123:Polyploidy; D012680:Sensitivity and Specificity; D014747:Vinblastine / Q000494:pharmacology
D001562:Benzimidazoles; D002219:Carbamates; D015342:DNA Probes; D003571:Cytochalasin B; D014747:Vinblastine; C006698:carbendazim; D003078:Colchicine