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Cancer Causes & Control

, Volume 3, Issue 3, pp 237–245 | Cite as

Heterogeneity in the clastogenic response to X-rays in lymphocytes from ataxia-telangiectasia heterozygotes and controls

  • John K. Wiencke
  • Diane W. Wara
  • John B. Little
  • Karl T. Kelsey
Research Papers

Abstract

A coded analysis of X-ray-induced chromatid aberrations in lymphocyte cultures from 45 control individuals and 19 ataxia-telangiectasia (A-T) heterozygotes was performed. The distribution of chromatid breaks induced in the late G2 portion of the cell cycle by 60 cGy of X-rays appeared bimodal in the study population. In six controls (13 percent) and in 12 of 19 (63 percent) A-T heterozygotes, the yields of X-ray-induced breaks observed were within the higher mode of the distribution. However, lymphocytes from A-T heterozygotes sensitive to the induction of chromatid breaks by 60 cGy did not contain increased numbers of aberrations following exposure to 20 cGy. The radio-resistant inhibition of DNA synthesis that occurs in A-T homozygotes was not observed in heterozygotes. Co-cultivation experiments showed an increased G2 delay in lymphocytes from an A-T heterozygote whose lymphocytes contained increased X-ray-induced chromatid breaks. The results show a significant association of A-T heterozygosity with G2 chromosomal sensitivity (P<0.001; Wilcoxon rank sum test). The measurement of X-ray-induced breaks, however, failed to identify 37 percent of A-T heterozygotes tested. The predicted prevalence of increased sensitivity to X-rays in controls is approximately three- to 30-fold greater than the estimated frequency of A-T heterozygotes in the general population. Therefore, although the increased sensitivity to X-ray-induced chromatid breaks appears to be associated with the A-T-gene, it is not a reliable indicator of A-T heterozygosity. Genetic or environmental factors other than the A-T gene also must be involved in the increased clastogenic response.

Key words

Ataxia telangiectasia chromosome breakage lymphocytes X-rays 

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Copyright information

© Rapid Communications of Oxford Ltd 1992

Authors and Affiliations

  • John K. Wiencke
    • 1
  • Diane W. Wara
    • 2
  • John B. Little
    • 3
  • Karl T. Kelsey
    • 3
  1. 1.Department of Epidemiology and Biostatistics and the Laboratory of Radiobiology and Environmental Health, School of MedicineUniversity of CaliforniaSan FranciscoUSA
  2. 2.Division of Pediatric Immunology and Rheumatology Division, School of MedicineUniversity of CaliforniaSan FranciscoUSA
  3. 3.Harvard UniversityLaboratory of Radiobiology, School of Public HealthBostonUSA

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