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Sex chromosomes, micronuclei and aging in women

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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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References

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Channarayappa, Ong T, Nath J (1992) Cytogenetic effect of vincristine sulfate and ethylene dibromide in human peripheral lymphocytes. Environ Mol Mutagen 20:117–126

    Google Scholar 

  • Degrassi F, Tanzarella C (1988) Immunofluorescent staining of kinetochores in micronuclei: a new assay for the detection of aneuploidy. Mutat Res 203:339–345

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Fenech M, Morley A (1985) The effect of donor age on spontaneous and induced micronuclei. Mutat Res 148:99–105

    Google Scholar 

  • Fenech M, Morley A (1989) Kinetochore detection in micronuclei: an alternative method for measuring chromosome loss. Mutagenesis 4:98–104

    Google Scholar 

  • Fitzgerald P (1975) A mechanism of X chromosome aneuploidy in lymphocytes of aging women. Humangenetik 28:153–158

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Ford J, Schultz C, Correll A (1988) Chromosome elimination in micronuclei: a common cause of hypoploidy. Am J Hum Genet 43:733–740

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Jacobs P (1963) Change of human chromosome count distribution with age: evidence for a sex difference. Nature 197:1080–1081

    Google Scholar 

  • Jacobs P, Court Brown W (1961) Distribution of human chromosome count in relation to age. Nature 191:1178–1180

    Google Scholar 

  • Jarvik L, Yen Fu-Sun, Moralishvili E (1974) Chromosome examinations in aging institutionalized women. J Gerontol 29:269–276

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Pierre R, Hoagland H (1973) Age-associated aneuploidy: loss of Y chromosome from human bone marrow cells with aging. Cancer 30:889–894

    Google Scholar 

  • 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

    Google Scholar 

  • 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

    Google Scholar 

  • Schneider E (1978) The genetics of aging. Plenum Publishing Corporation, New York, New York, pp 27–52

    Google Scholar 

  • 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

    Google Scholar 

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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

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