Open Access

G2-checkpoint abrogation in irradiated lymphocytes: A new cytogenetic approach to assess individual radiosensitivity and predisposition to cancer

  • Authors:
    • Georgia I. Terzoudi
    • Vasiliki I. Hatzi
    • Katarzyna Barszczewska
    • Kalliopi N. Manola
    • Chryssa Stavropoulou
    • Philip Angelakis
    • Gabriel E. Pantelias
  • View Affiliations

  • Published online on: November 1, 2009     https://doi.org/10.3892/ijo_00000439
  • Pages: 1223-1230
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Abstract

Increased yield of chromatid breaks, following in vitro G2-phase lymphocyte irradiation, can be a marker of individual radiosensitivity and cancer predisposing genes whose role is to respond to DNA damage. Mutations or polymorphisms of genes encoding DNA repair pathways may underlie the increased chromosomal radiosensitivity. However, genes that facilitate DNA damage recognition, using signal transduction pathways to activate cell cycle arrest and preserve genomic integrity, are perhaps the most important determinant. Based on the latter hypothesis, an individual radiosensitivity parameter (IRP) is introduced, which expresses, at individual level, the G2-checkpoint potential to facilitate DNA damage recognition and repair of radiation-induced chromosomal damage during G2 to M-phase transition. Based on this parameter a new methodology for assessment of individual radiosensitivity is proposed, which involves G2-checkpoint abrogation by caffeine to obtain the IRP values. To evaluate the proposed methodology, blood samples from 52 healthy donors were taken for inter-individual radiosensitivity analysis using both the conventional G2 chromosomal radiosensitivity assay as well as the new approach using caffeine-induced G2-checkpoint abrogation. The two assays were compared in experiments using samples from 5 hypersensitive patients, 3 AT-homozygotes, 3 AT-heterozygotes, and the GM15786, GM03188A, GM09899, HCC1937 and MCF-7 cell lines. Using the G2 chromosomal radiosensitivity assay, donors are predicted as G2 radiosensitive or normal, while according to the new approach, individuals can be classified as highly radiosensitive, radiosensitive, normal, radioresistant and highly radioresistant. Overall, the new approach provides better individual radiosensitivity discrimination and intra-experimental reproducibility. Therefore, the proposed methodology using IRP values may provide a clinically applicable predictive assay for individual radiosensitivity and predisposition to cancer.

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November 2009
Volume 35 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Terzoudi GI, Hatzi VI, Barszczewska K, Manola KN, Stavropoulou C, Angelakis P and Pantelias GE: G2-checkpoint abrogation in irradiated lymphocytes: A new cytogenetic approach to assess individual radiosensitivity and predisposition to cancer. Int J Oncol 35: 1223-1230, 2009
APA
Terzoudi, G.I., Hatzi, V.I., Barszczewska, K., Manola, K.N., Stavropoulou, C., Angelakis, P., & Pantelias, G.E. (2009). G2-checkpoint abrogation in irradiated lymphocytes: A new cytogenetic approach to assess individual radiosensitivity and predisposition to cancer. International Journal of Oncology, 35, 1223-1230. https://doi.org/10.3892/ijo_00000439
MLA
Terzoudi, G. I., Hatzi, V. I., Barszczewska, K., Manola, K. N., Stavropoulou, C., Angelakis, P., Pantelias, G. E."G2-checkpoint abrogation in irradiated lymphocytes: A new cytogenetic approach to assess individual radiosensitivity and predisposition to cancer". International Journal of Oncology 35.5 (2009): 1223-1230.
Chicago
Terzoudi, G. I., Hatzi, V. I., Barszczewska, K., Manola, K. N., Stavropoulou, C., Angelakis, P., Pantelias, G. E."G2-checkpoint abrogation in irradiated lymphocytes: A new cytogenetic approach to assess individual radiosensitivity and predisposition to cancer". International Journal of Oncology 35, no. 5 (2009): 1223-1230. https://doi.org/10.3892/ijo_00000439