Abstract
Several studies on aneuploidy and aging have shown a significant increase in the loss of chromosomes in both males and females with age. Others have observed a significant increase in micronucleus formation in lymphocytes with age. The objectives of this investigation were to determine the relationship between sex chromosome loss and increased micronucleus frequencies with age, to establish sex chromosome loss frequencies unbiased by cellular survival factors or slide preparation, and to determine the effect of smoking on sex chromosome loss. Blood samples were obtained from 8 newborn females and 38 adult females ranging in age from 19 to 77. Isolated lymphocytes were cultured according to standard techniques and blocked with cytochalasin B. Two thousand binucleated cells per donor were scored using a modified micronucleus assay to determine the kinetochore status of each micronucleus. Slides were then hybridized with a 2.0 kb centromeric X chromosome-specific probe labeled with biotinylated dUTP, and detected with fluorescein-conjugated avidin. All micronucleated cells were relocated and their X chromosome status was determined. We found the X chromosome to be present in 72.2% of the micronuclei scored; additionally our results show a significant increase with age in the number of micronuclei containing an X chromosome.
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Abruzzo M, Mayer M, Jacobs P (1985) Aging and aneuploidy: evidence for the preferential involvement of the inactive X chromosome. Cytogenet Cell Genet 39:275–278
Antoccia A, Degrassi F, Battistoni A, Ciliutti P, Tanzarella C (1991) In vitro micronucleus test with kinetochore staining: evaluation of test performance. Mutagenesis 6:319–324
Bernat R, Delannoy M, Rothfield N, Earnshaw W (1991) Disruption of centromere assembly during interphase inhibits kinetochore morphogenesis and function in mitosis. Cell 66: 1229–1238
Channarayappa, Ong T, Nath J (1992) Cytogenetic effect of vincristine sulfate and ethylene dibromide in human peripheral lymphocytes. Environ Mol Mutagen 20:117–126
Degrassi F, Tanzarella C (1988) Immunofluorescent staining of kinetochores in micronuclei: a new assay for the detection of aneuploidy. Mutat Res 203:339–345
Eastmond D, Tucker JD (1989 a) Identification of aneuploidy inducing agents using cytokinesis-blocked human lymphocytes and an antikinetochore antibody. Environ Mol Mutagen 13: 34–43
Eastmond D, Tucker JD (1989 b) Kinetochore localization in micronucleated cytokinesis-blocked Chinese hamster ovary cells: a new and rapid assay for identifying aneuploidy-inducing agents. Mutat Res 224:517–525
Fenech M, Morley A (1985) The effect of donor age on spontaneous and induced micronuclei. Mutat Res 148:99–105
Fenech M, Morley A (1989) Kinetochore detection in micronuclei: an alternative method for measuring chromosome loss. Mutagenesis 4:98–104
Fitzgerald P (1975) A mechanism of X chromosome aneuploidy in lymphocytes of aging women. Humangenetik 28:153–158
Fitzgerald P (1983) Premature centromere division of the X chromosome, in Sandberg A (ed) Cytogenetics of the mammalian X chromosome. Part B. X chromosome anomalies and their clinical manifestations. Liss, New York, pp 171–184
Fitzgerald P, McEwan C (1977) Total aneuploidy and age-related sex chromosome aneuploidy in cultured lymphocytes of normal men and women. Hum Genet 39:329–337
Ford J, Schultz C, Correll A (1988) Chromosome elimination in micronuclei: a common cause of hypoploidy. Am J Hum Genet 43:733–740
Galloway S, Buckton K (1978) Aneuploidy and aging: chromosome studies on a random sample of the population using G-Banding. Cytogenetic Cell Genet 20:78–95
Hennig U, Rudd N, Hoar D (1988) Kinetochore immunofluorescence in micronuclei: a rapid method for the in situ detection of aneuploidy and chromosome breakage in human fibroblasts. Mutat Res 203:405–414
Jacobs P (1963) Change of human chromosome count distribution with age: evidence for a sex difference. Nature 197:1080–1081
Jacobs P, Court Brown W (1961) Distribution of human chromosome count in relation to age. Nature 191:1178–1180
Jarvik L, Yen Fu-Sun, Moralishvili E (1974) Chromosome examinations in aging institutionalized women. J Gerontol 29:269–276
Johnson GD, Nogueira Araujo GM de C (1981) A simple method of reducing the fading of immunofluorescence during microscopy. J Immunol Methods 43: 349–350
Mitchell A, Jeppesen P, Hanratty D, Gosden J (1992) The organisation of repetitive DNA sequences on human chromosomes with respect to the kinetochore analysed using a combination of oligonucleotide primers and CREST anticentromere serum. Chromosoma 101:333–341
Nakagome Y, Abe T, Misawa S, Takeshita T, Iinuma K (1984) The loss of centromeres from chromosomes of aged women. Am J Hum Genet 36:398–404
Pierre R, Hoagland H (1973) Age-associated aneuploidy: loss of Y chromosome from human bone marrow cells with aging. Cancer 30:889–894
Pinkel D, Landegent J, Collins C, Fuscoe J, Segraves R, Lucas J, Gray J (1988) Fluorescence in situ hybridization with human chromosome-specific libraries: detection of trisomy 21 and translocations of chromosome 4. Proc Natl Acad Sci USA 85:9138–9142
Richard F, Aurias A, Couturier J, Dutrillaux A, Herard A, Gerbault-Seureau M, Hoffschir F, Lamoliatte E, Lefrancois D, Lombard M, Muleris M, Prieur M, Ricoul M, Sabatier L, Viegas-Pequignot E, Volobouev V, Dutrilaux B (1993) Aneuploidy in human lymphocytes: an extensive study of eight individuals of various ages. Mutat Res 295:71–80
Schneider E (1978) The genetics of aging. Plenum Publishing Corporation, New York, New York, pp 27–52
Willard H, Smith K, Sutherland J (1983) Isolation and characterization of a major tandem repeat family from the human X chromosome. Nucleic Acids Res 11:2017–2033
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Hando, J.C., Nath, J. & Tucker, J.D. Sex chromosomes, micronuclei and aging in women. Chromosoma 103, 186–192 (1994). https://doi.org/10.1007/BF00368011
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DOI: https://doi.org/10.1007/BF00368011