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. 2003 Apr 22;88(8):1251-5.
doi: 10.1038/sj.bjc.6600897.

Radiation-hypersensitive cancer patients do not manifest protein expression abnormalities in components of the nonhomologous end-joining (NHEJ) pathway

T Leong  1 , M Chao, S Bassal, M McKay
Affiliations

Radiation-hypersensitive cancer patients do not manifest protein expression abnormalities in components of the nonhomologous end-joining (NHEJ) pathway

T Leong et al. Br J Cancer. .

Abstract

Radiation therapy (RT) is utilised for the treatment of around half of all oncology patients during the course of their illness. Despite great clinical progress in the rational deployment of RT, the underlying molecular basis for its efficacy and toxicity are currently imperfectly understood. In this study, we took a biochemical approach to evaluate the potential role of key ionising radiation repair proteins in the treatment outcomes of patients with severe acute or late RT side effects. Lymphoblastoid cell lines were established from blood samples from 36 radiosensitive cases and a number of controls (the latter had had RT but did not develop significant toxicity). The expression level and migration of key proteins from the nonhomologous end-joining (NHEJ) pathway was evaluated by Western blot analysis on cases and controls. We did not observe any abnormalities in expression level or migration pattern of the following NHEJ proteins in radiosensitive cancer cases: Ku70, Ku80, XRCC4, DNA Ligase IV. These important negative results provide evidence that mutations that affect protein expression of these NHEJ components are unlikely to underlie clinical radiation sensitivity.

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Figures

Figure 1
Figure 1
Photograph showing an example of a severe late radiation reaction. This patient (patient 8 in Table 1 ) developed severe fibrosis, retraction and telangiectasia of the breast following routine postoperative RT for breast cancer.
Figure 2
Figure 2
Typical Western blot analysis of protein extracts from radiosensitive patients using (A) anti-DNA ligase IV, (B) anti-XRCC4, (C) anti-Ku70 and (D) anti-Ku80 antibodies. There were no differences in expression for any of the four proteins between radiosensitive and control patients. Gamma-tubulin was used as an internal control to adjust for differences in the amount of protein loaded in each lane (lower autoradiograph in each panel). P=radiosensitive patient, C=control patient.
See this image and copyright information in PMC

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