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Nonrandom distribution of mutagen-induced chromosome breaks in lymphocytes of patients with different malignancies
Authors:Dave B  Hsu T  Hong W  Pathak S
Institution:UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT CELL BIOL,CELLULAR GENET LAB,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT THORAC HEAD & NECK MED ONCOL,HOUSTON,TX 77030.
Abstract:Data regarding specific chromosomal alterations in most solid neoplasms are scarce because the complex changes observed in tumor biopsies are often a challenge to interpret. The present investigation using chromosomal banding, was designed to analyze exact regions of spontaneous and mutagen-induced lymphocytic chromosomal breaks and investigate if they are unique for different cancers. Tissue from three groups of individuals were included in the study, viz., normal individuals, untreated head and neck cancer patients, and untreated melanoma patients. For every individual three samples were analyzed for spontaneous, bleomycin (radiomimetic)-induced and 4-nitroquinoline-N-oxide(4NQO) (ultraviolet rays mimetic)-induced chromosome damage. The results revealed that in melanoma patients, chromosomes 1, 6, and 9 showed a significantly higher number of breaks than other chromosomes. A clustering of breaks was observed at loci 1p32, 1q32, 6p21, 6q21 and 9q11. Among the head and neck cancer patients, a significantly larger number of breaks was found in chromosomes 3 and 7 with clustering of breaks mainly in regions 3p21, 3q21, 7q22 and 7q32. Thus, it was found that regardless of the mutagen used, specific chromosomes are more susceptible to breakage than others. Our results indicate that chromosomal fragility is specific for particular cancers and that challenging the cells with mutagens reveals it at a more pronounced rate. Mutagen-induced chromosome breaks appear to be nonrandom affecting different chromosomes in different cancers. Clustering of breaks that occur in specific regions of these chromosomes might provide definite clues for molecular analysis and further in-depth studies of cancer predisposed individuals.
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