Detection of chromosomal breakage in the 1cen-1q12 region of interphase human lymphocytes using multicolor fluorescence in situ hybridization with tandem DNA probes.

A novel multicolor fluorescence in situ hybridization approach, using an alpha satellite probe which labels the centromeric region on chromosome 1 and a classical satellite probe which targets an adjacent breakage-prone region (1q12), has been used to detect both hyperdiploidy and chromosome breakage in interphase human cells. With the use of this technique significant increases in chromosomal breakage were observed in interphase and metaphase lymphocytes irradiated in vitro. Metaphase analysis indicated that a significant proportion of these breakage events represented potentially stable aberrations such as translocations and inversions. A comparison of frequencies using a single classical satellite probe and the adjacent alpha and classical satellite probes indicated that this tandem label procedure allowed chromosomal breakage to be detected and distinguished from hyperdiploidy in untreated interphase lymphocytes, indicating the potential of this procedure for human biomonitoring. To determine whether this hybridization approach could detect alterations in humans, peripheral blood lymphocytes were obtained from a group of pesticide applicators and mixers and compared with a nonexposed control group. Significant increases in both hyperdiploidy and chromosomal breakage affecting the labeled region on chromosome 1 were observed in the pesticide-exposed group. These results indicate that this hybridization strategy allows hyperdiploidy and chromosomal breakage to be detected rapidly in interphase human cells and may facilitate the detection of chromosomal alterations in human populations exposed to carcinogenic and genotoxic agents using tissues which have not been previously amenable for cytogenetic analysis.