Chromosomes of Older Humans Are More Prone to Aminopterine-Induced Breakage

Esposito, D., Fassina, G., Szabo, P., Deangelis, P., Rodgers, L., Weksler, M., Siniscalco, M. (February 1989) Chromosomes of Older Humans Are More Prone to Aminopterine-Induced Breakage. Proceedings of the National Academy of Sciences of the United States of America, 86 (4). pp. 1302-1306. ISSN 0027-8424

URL: http://www.ncbi.nlm.nih.gov/pubmed/2919179

Abstract

We have adopted a simplified version of the "cell hybrid cotransfer method" to test the hypothesis that human lymphocytes derived from elderly individuals have a higher chromosome instability. Peripheral blood lymphocytes from "old" male individuals and "young" controls were fused with a Chinese hamster cell line (CHO-YH21), yielding 10 HAT-resistant rodent-human clones from the old propositi and 22 from the young controls (HAT = hypoxanthine/aminopterin/thymidine). Both series of hybrid clones were analyzed with respect to the retention of the enzyme glucose-6-phosphate dehydrogenase and the surface antigen MIC2 identified by monoclonal antibody 12E7, two human X chromosome-linked markers located at opposite ends of the X chromosome. Cell hybrid clones with an X chromosome from a young control retained both markers in about 70% of the cells. In contrast, cell hybrid clones with an X chromosome from an old donor retained the MIC2 marker in only 30% of their cells. Slot-blot hybridization studies have established that the observed loss of the MIC2 marker is due to loss of the coding gene, not to suppression of its expression. Similar hybridization studies with molecular probes specific for other regions of the X chromosome suggest preferential chromosomal breakage sites. T lymphocytes from old donors were also found to have an LD50 for aminopterine significantly lower than the concentration of this drug in the HAT medium used to grow the hybrids, suggesting that the higher level of gene loss observed in the X chromosomes from old donors may be directly related to their increased sensitivity to the clastogenic effect of aminopterine. We speculate that the higher rate of chromosomal breakage and of marker loss observed along the "old-age" X chromosomes could be the result of "molecular scars" accumulated with aging at sites of constitutive chromosomal fragility.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > chromosomes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene silencing
CSHL Authors:
Communities: CSHL labs
Depositing User: Gail Sherman
Date: February 1989
Date Deposited: 28 Jul 2017 16:32
Last Modified: 28 Jul 2017 16:32
PMCID: PMC286676
Related URLs:
URI: http://repository.cshl.edu/id/eprint/34846

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