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Delayed chromosomal instability induced by DNA damage

B A Marder1, W F Morgan

  • 1Laboratory of Radiobiology and Environmental Health, University of California, San Francisco 94143-0750.

Molecular and Cellular Biology
|November 1, 1993
PubMed
Summary
This summary is machine-generated.

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Ionizing radiation can cause delayed genomic instability, leading to chromosome rearrangements and cell death. This study observed delayed chromosomal instability in hamster-human hybrid cells after X-ray exposure, suggesting a link to reproductive cell death.

Area of Science:

  • Genetics
  • Radiation Biology
  • Cell Biology

Background:

  • Ionizing radiation (e.g., X-rays) induces DNA damage, potentially leading to mutations, chromosomal aberrations, and cell death.
  • While immediate effects are known, accumulating evidence suggests delayed genomic instability can manifest generations after radiation exposure.

Purpose of the Study:

  • To investigate delayed chromosomal instability following X-ray exposure.
  • To examine the relationship between delayed chromosomal instability and delayed reproductive cell death.

Main Methods:

  • Utilized a hamster-human hybrid cell line.
  • Employed fluorescence in situ hybridization to analyze metaphase cells several generations post-irradiation.
  • Assessed chromosomal rearrangements and reproductive cell death (plating efficiency).

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Main Results:

  • Delayed chromosomal instability, characterized by rearrangements of human chromosome 4, was observed in 29% (5 Gy) and 62% (10 Gy) of surviving colonies.
  • A correlation was found between delayed chromosomal instability and reduced plating efficiency, suggesting a role in cytotoxicity.
  • Chromosomal instability was not apparent at the sister chromatid exchange endpoint.

Conclusions:

  • X-ray exposure can induce delayed chromosomal instability in surviving cells, manifesting in subsequent generations.
  • Chromosome rearrangements likely contribute to delayed reproductive cell death following radiation.
  • Mechanisms involving chromosome fusion, breakage, and refusion may underlie the observed delayed instability.