FLUORESCENCE IN-SITU HYBRIDIZATION 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. F or the aneuploidy events, centromeric probes for 6 selected chromosome s (1, 8, X, 11, 17, 18) were used to measure chromosome loss, addition and non-disjunction in the interphase nuclei of these binucleate cell s. The chromosomes were probed in pairs using Cy-3 (red) and FITC (gre en) labels for the 2 different centromeric regions. For colchicine, th e total non-disjunction frequencies for chromosomes 1 and 8 were simil ar to the total micronucleus frequencies, but were detected as signifi cant at lower concentrations. For vinblastine (chromosomes 1 and 8) an d carbendazim (all 6 chromosomes) the frequencies of non-disjunction f ar exceeded (7 and > 2-fold, respectively) the peak frequencies of mic ronucleus induction. Although most chromosomes exhibited similar sensi tivity in all the aneuploidy events measured, there was an indication that chromosome X was more than susceptible to non-disjunction than th e other chromosomes. We believe that measurement of non-disjunction in binucleate human lymphocytes using chromosome specific centromeric pr obes offers a sensitive method for detection of aneuploidy and is part icularly appropriate for the establishment of thresholds.