Sequentially-induced responses define tumour cell radiosensitivity

Jerry R. Williams, Yonggang Zhang, Haoming Zhou, Daila S. Gridley, Cameron J. Koch, James M. Slater, John F. Dicello, John B. Little

Research output: Contribution to journalArticle

Abstract

Purpose: Our aim was to define dose-dependent and genotype-dependent components of radiosensitivity by resolving patterns of radiation-induced clonal inactivation into specific responses. Methods: In a set of 10 tumour cells with varying expression of radiosensitivity and genotype, we identified doses at which all tumour cells change in their rate of clonogenic inactivation. We tested intervening dose-segments as to whether inactivation was constant, expressing inactivation as a log-linear function of dose. We compared these segments to components proposed in the Hit-target (HT) model and the Linear-quadratic (LQ) model. Temporal changes in redistribution in cell-cycle prevalence and apoptosis were examined as essential components of cellular radiosensitivity. Results: We identified four distinct responses induced sequentially in all cells independent of genotype. Rates of inactivation within each response varied with expression of genotype and identified: (i) A hypersensitive component H (0.0-0.10 Gy); (ii) a resistant component R (0.1-0.2 Gy); (iii) an induced repair response alpha* (0.2 Gy and higher); and (iv) a more sensitive component omega* (3.0 Gy and higher). The H, alpha* and omega* components were fitted well by log-linear patterns, the R response did not. Conclusions: Four distinct, sequentially-induced responses comprise cellular radiosensitivity. H and R responses are associated with low dose hyper-radiosensitivity and early apoptosis, while the alpha* and omega* responses share characteristics of the HT and LQ models and are associated with post-repair apoptosis. Radiation induces these four responses at the same doses in all cells, but the rate of inactivation over each response depends on genotype.

Original languageEnglish (US)
Pages (from-to)628-643
Number of pages16
JournalInternational journal of radiation biology
Volume87
Issue number6
DOIs
StatePublished - Jun 1 2011

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Keywords

  • 14-3-3σ
  • ATM
  • CDKN1A
  • TP53
  • apoptosis
  • chromosomal aberrations
  • clonal radiosensitivity
  • colorectal tumours
  • glioblastoma tumours
  • models of radiosensitivity

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

Cite this

Williams, J. R., Zhang, Y., Zhou, H., Gridley, D. S., Koch, C. J., Slater, J. M., Dicello, J. F., & Little, J. B. (2011). Sequentially-induced responses define tumour cell radiosensitivity. International journal of radiation biology, 87(6), 628-643. https://doi.org/10.3109/09553002.2011.568573