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Radiation induced chromosomal instability in human T-lymphocytes
B Lambert1, K Holmberg, P Hackman
1The Karolinska Institute, Department of Biosciences, CNT/Novum, 141 57, Huddinge, Sweden. bo.lambert@cnt.ki.se
Mutation Research
|September 28, 1998
Summary
Chromosomal instability, a hallmark of cancer, can be induced by radiation in human lymphocytes. This instability manifests as new chromosomal aberrations in cell generations long after irradiation, independent of dose rate or recovery time.
Area of Science:
- Cell Biology
- Genetics
- Radiation Biology
Background:
- Chromosomal instability (CIN) is a hallmark of cancer, characterized by increased chromosomal aberrations and rearrangements.
- Previous studies indicate that radiation, regardless of linear energy transfer (LET), can induce CIN.
- The precise mechanisms and conditions leading to radiation-induced CIN in human cells remain under investigation.
Purpose of the Study:
- To investigate the characteristics of chromosomal instability in primary human lymphocytes following gamma irradiation.
- To determine the influence of radiation dose rate and post-exposure recovery on the development of CIN.
- To assess whether microsatellite instability is associated with chromosomal instability in irradiated human T-lymphocytes.
Main Methods:
- Primary human G0-lymphocytes were exposed to gamma irradiation at high (45 Gy/h) and low (0.024 Gy/h) dose rates.
- Clonal progeny of irradiated lymphocytes were analyzed for chromosomal aberrations over successive generations.
- T-cell clones were assessed for chromosomal aberrations, cloning ability, sensitivity to re-irradiation, and microsatellite instability (CA-repeat length variation).
Main Results:
- A typical feature of CIN was the appearance of novel chromosomal aberrations in the clonal progeny of irradiated lymphocytes, persisting over many generations.
- This CIN phenotype was observed irrespective of the radiation dose rate (high vs. low) or a 5-day recovery period in G0.
- No persistent decrease in cloning ability or altered sensitivity to a second radiation exposure was noted. Microsatellite instability was not increased in X-irradiated T-cell progeny.
Conclusions:
- Chromosomal instability can be induced in human lymphocytes by gamma irradiation, manifesting as novel aberrations in subsequent cell generations.
- The development of radiation-induced CIN in these cells is not critically dependent on acute genotoxic stress from high dose rates or a conflict between growth stimulation and radiation damage.
- Microsatellite instability is not a component of the chromosomal instability phenotype in human T-lymphocytes.