Cell cycle dependent aneuploidy induction by X-rays in vitro in human lymphocytes

Area of Science:

• Radiation biology
• Cytogenetics
• Molecular biology

Background:

• Ionizing radiation primarily causes DNA strand breaks and chromosomal aberrations.
• Evidence suggests ionizing radiation may also induce numerical chromosome aberrations (aneuploidy).
• A clear mechanism for radiation-induced aneuploidy remains undefined.

Purpose of the Study:

• To investigate the relative sensitivity of G1 and G2 cell cycle phases to X-ray induced aneuploidy.
• To assess the dose-dependent induction of centromere-positive micronuclei in different cell cycle phases.

Main Methods:

• Human lymphocytes from whole blood cultures were irradiated in vitro with X-rays (0.5, 1, 2 Gy).
• Cells were harvested at different time points (70, 74, 78 hours) after cytochalasin-B blockade to analyze binucleated cells.
• Centromere-positive micronuclei were quantified using a specific oligonucleotide probe to distinguish whole chromosome losses.

Main Results:

• The frequency of centromere-positive micronuclei ranged from 5% to 18%, varying with cell cycle stage and radiation dose.
• Lymphocytes exposed during the G1 phase showed a higher frequency of centromere-positive micronuclei compared to those exposed in G2.
• A dose-effect relationship for centromere-positive micronuclei was observed following G1 exposure, but not G2 exposure.

Conclusions:

• The G1 phase appears to be a more sensitive target than G2 for X-ray induced aneuploidy.
• Differences in centromere-positive micronuclei yields between G1 and G2 phases suggest distinct cellular targets or repair mechanisms.
• Further research is needed to elucidate the specific mechanisms underlying radiation-induced aneuploidy in different cell cycle phases.