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Age-associated micronuclei, kinetochores and sex chromosome loss in men

Journal Article · · Environmental and Molecular Mutagenesis
OSTI ID:115141
;  [1];  [2]
  1. West Virginia Univ., Morgantown, WV (United States)
  2. Lawrence Livermore National Laboratory, CA (United States)
Studies on aneuploidy have shown a significant increase in the loss of chromosomes in both males and females with age and also a significant increase in micronucleus formation in lymphocytes with age. This study attempted (1) to ascertain whether the age-associated increase in Y chromosome loss and micronucleus formation are related. (2) to determine whether there is a correlation between Y chromosome-negative metaphase cells and Y chromosome-positive micronuclei from the same donors, and (3) to determine the relationships among the kinetochore status of micronuclei, Y chromosome-positive micronuclei, and age. Blood samples were obtained from thirty-five healthy males ranging in age from 22 to 79 years, and from the umbilical cords of eighteen newborn males. Two thousand binucleated cells were scored per sample. The kinetochore status of each micronucleus was recorded. Slides were then hybridized with the Y chromosome specific probe pHY10, labeled with biotinylated dUTP, and visualized with fluorescein conjugated avidin. All micronucleated cells were relocated and scored as Y+ or Y- depending on their Y probe status. A total of 303 micronuclei were scored, of which 41 (13.5%) contained the Y chromosome. ANOVA shows a significant increase in the number of Y chromosome-positive micronuclei with age (p<0.001). Of the 41 Y+ micronuclei 36 (87.8%) were kinetochore negative, suggesting a relationship between the absence of kinetochore function and micronucleus formation. Also, 500 metaphase spreads per sample were scored for the Y chromosome, showing an increase in Y-cells with age (p<0.001). A correlation analysis between Y chromosome-positive micronuclei and Y chromosome-negative metaphase cells resulted in a correlation coefficient of 0.71 (p.005).
DOE Contract Number:
W-7405-ENG-48
OSTI ID:
115141
Report Number(s):
CONF-9503160--
Journal Information:
Environmental and Molecular Mutagenesis, Journal Name: Environmental and Molecular Mutagenesis Journal Issue: Suppl.25 Vol. 25; ISSN EMMUEG; ISSN 0893-6692
Country of Publication:
United States
Language:
English

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