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British Journal of Radiology (2006) 79, 510-517
© 2006 British Institute of Radiology
doi: 10.1259/bjr/83726649
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Clinical and cellular ionizing radiation sensitivity in a patient with xeroderma pigmentosum

C F Arlett, PhD1, P N Plowman, MD, FRCP, FRCR2, P B Rogers, MB BS, MRCP, FRCR2, C N Parris, PhD3, F Abbaszadeh, MSc3, M H L Green, PhD4, T J McMillan, PhD5,6, C Bush, BSc6, N Foray, PhD7 and A R Lehmann, PhD1

1 Genome Damage & Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, , 2 Radiotherapy/Clinical Oncology, St Bartholomew's Hospital, 25 Bartholomew Close, West Smithfield, London EC1A 7BE, , 3 Division of Biosciences, School of Health Sciences and Social Care, Brunel University, Kingston Lane, Uxbridge, Middlesex UP8 3PH, , 4 School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockcroft Building, Lewes Road, Brighton BN2 4GJ, , 5 Institute of Environmental and Natural Sciences, Faraday Building, Lancaster University, Lancaster LA1 4YA, , 6 The Institute of Cancer Research, Royal Cancer Hospital, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK, , 7 INSERM U647, ID17, European Synchrotron Research Facility, Rue Jules Horowitz, BP220 – 38043 Grenoble, France,


Figure 1
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  		Figure 1. The irradiated scalp portal. The irradiated skin remained depilated and became frankly ulcerated and necrotic in the operation wound site.

 

Figure 2
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  		Figure 2. CT brain scan demonstrating widespread hemispheric oedema beneath the irradiated portal. Noteworthy is the widespread extent of the oedema throughout the hemisphere, not withstanding the restricted portal size, the moderate prescription dose(38 Gy) and the low energy electron portal (6 MEV) – that had to penetrate bone first. It was this unrelenting cerebral oedema, emanating from radio necrosis of brain under the radiation portal, that caused death.

 

Figure 3
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  		Figure 3. Ultraviolet radiation below 280 nm (UVC) clonal survival of XP14BR fibroblasts. Key: Figure 3XP14BR.1 (biopsy 1); Figure 3XP14BR.2 (biopsy 2, mean ± standard error of 4 experiments). Normal fibroblast lines: Figure 31BR.3 (mean ± standard error of 3 experiments), Figure 3142BR, Figure 3250BR, Figure 3251BR. Additional XP cell lines: Figure 3XP15BR, Figure 3XP23BE. Single experiments except where indicated.

 

Figure 4
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  		Figure 4. Ionizing radiation clonal survival of XP14BR fibroblasts. Key as forFigure 3Go: Additional XP line; Figure 4XP233VA; Ataxia telangiectasia fibroblast lines; Figure 4AT1BR; Figure 4AT2BR. Means ± standard error based on numbers of experiments as follows: XP14BR.1, 1; XP14BR.2, 6; 1BR.3, 58; 142BR, 8; 250BR, 4; 251BR, 13; XP23BE, 2; XP233VA, 2; AT1BR, 5; AT2BR, 3.

 

Figure 5
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  		Figure 5. Nitrogen mustard sensitivity of SV40 transformed XP14BR fibroblasts. Key: Figure 5XP14BRneo17; Normal transformed fibroblast lines; Figure 5MRC5V1; Figure 5GM0637; Figure 51BR.3-G. Means ± standard error of 2–4 experiments.

 

Figure 6
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  		Figure 6. DNA double strand break(DSB) repair rate after 30 Gy delivered at 4°C. Repair data are expressed as the fraction of radiation-induced DNA fragments (FAR) migrating in the gel that remained at the indicated repair times. Each point represents the mean ± standard error of at least three replicate experiments. Key: Figure 6XP14BR.2; Figure 6149BR, Normal non-transformed fibroblast line.

 

Figure 7
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  		Figure 7. Rate of repair of chromosome breaks after 6 Gy delivered at 4°C. Repair data are expressed as percentage of premature chromosome condensation fragments in excess (ECF) at the repair times indicated. Each point represents the mean ± standard error of at least three replicate experiments. Key: Figure 7XP14BR.2; Figure 7149BR, Normal non-transformed fibroblast line.

 

Figure 8
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  		Figure 8. Immunoblotting for the C-terminal end of the XPC protein. Lanes 1 and 2, T921A, T943A (transfectants); lane 3, XP14BRneo17 (recipient); lane 4, MRC5V1 (control); lanes 5 and 6, T941B and T948B (transfectants). Upper panel, 20 s exposure, lower panel, 5 min exposure.

 

Figure 9
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  		Figure 9. Ultraviolet radiation below 280 nm (UVC) sensitivity of XP14BRneo17 and its transfectants. Means ± standard error of the number of experiments indicated. Key: Figure 9XP14BRneo17 (non-transfected, 1 expt); Figure 9T921A (2 expts); Figure 9T943A (4 expts); Figure 9T941B (2 expts) (all transfectants); Figure 9MRC5V1 (1 expt); Figure 9GM0637 (2 expts).

 

Figure 10
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  		Figure 10. Ionizing radiation sensitivity of XP14BR, XP14BRneo17, and transfectants. Means± standard error of the number of experiments indicated. A. Effect of SV40 transformation on radiosensitivity. Key: Figure 10XP14BR (6 expts); Figure 10XP14BRneo17 (1 expt); Figure 101BR.3 (58 expts); Figure 101BR.3neo (4 expts); Figure 10142BR (8 expts); Figure 10142BRneo (3 expts); Figure 10MRC5 (1 expt); Figure 10MRC5V1 (2 expts). B. Comparison of transfectants with XP14BRneo17. Key: Figure 10XP14BRneo17 (1 expt); Figure 10T921A (2 expts); Figure 10T943A (3 expts); Figure 10T941B (2 expts); Figure 10T948B (1 expt).

 




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