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British Journal of Radiology (2008) 81, 51-58
© 2008 British Institute of Radiology
doi: 10.1259/bjr/27072321
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Full paper

Minimal ionizing radiation sensitivity in a large cohort of xeroderma pigmentosum fibroblasts

C F Arlett, PhD1, M H L Green, PhD2, P B Rogers, MB, BS, MRCP, FRCR3*, A R Lehmann, PhD1 and P N Plowman, MD, FRCP, FRCR3

1 Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, BN1 9RQ, 2 School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockcroft Building, Lewes Road, Brighton, BN2 4GJ, 3 Radiotherapy/Clinical Oncology, St. Bartholomew's Hospital, 25 Bartholomew Close, West Smithfield, London, EC1A 7BE, UK

Correspondence: C F Arlett, Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, BN1 9RQ, UK. E-mail: colin-a{at}solutions-inc.co.uk; GDSC{at}sussex.ac.uk


   Abstract
Top
 Abstract
Introduction
 Methods and materials
 Results
 Discussion
 References
 
We have examined our ionizing radiation survival data for 33 xeroderma pigmentosum (XP) primary fibroblast lines and compared the data to that of 53 normal fibroblast lines, 7 Cockayne syndrome (CS) lines, 4 combined XP/CS lines and 8 ataxia-telangiectasia fibroblast lines. Although there are differences in radiosensitivity between cell lines within each class, we have no convincing evidence that XP lines as a group are more sensitive to ionizing radiation than the general population. However, because the XP phenotype may lead to premature ageing, especially of sun-exposed tissues, we would still advocate caution when XP patients come to radiotherapy. Our results confirm the extreme ionizing radiation hypersensitivity of ataxia-telangiectasia; they are also consistent with a tendency for slight hypersensitivity in CS, but not (necessarily) in combined XP/CS.


   Introduction
Top
 Abstract
 Introduction
Methods and materials
 Results
 Discussion
 References
 
We recently reported on a patient with the DNA repair-defective, sun-sensitive, cancer-prone syndrome xeroderma pigmentosum (XP) [1] who showed extreme sensitivity to ionizing radiation and ultimately died following radiotherapy [2, 3]. Although in the case of this patient, the ionizing radiation sensitivity appeared not to be associated with her ultraviolet (UV) sensitivity [3], it has led us to explore the suspicion, first noted in the 1920s [4–6], that ionizing radiation hypersensitivity is more prevalent among XP patients than among the general population.

Ionizing radiation produces DNA double-strand breaks and complex lesions, DNA single-strand breaks and a wide variety of oxidative base damage [7, 8]. Nearly all the base damage is repaired via the process of base excision repair, in which the first step is the cleavage of the glycosylic bond between the damaged base and the deoxyribose sugar. Patients with XP are not deficient in the glycosylases that mediate base excision repair. Seven XP complementation groups (A–G) have been associated with components of the nucleotide excision repair (NER) pathway [1, 9]. An eighth gene codes for a DNA polymerase ({eta}, eta), which can bypass UV lesions on a damaged DNA template [10, 11].

Cell killing via ionizing radiation is primarily due to DNA double-strand breaks, and so patients with XP would be expected to show normal repair proficiency. Thus, XP patients would not be expected a priori to be hypersensitive to ionizing radiation. Nevertheless, cellular hypersensitivity to the lethal effects of ionizing radiation has been reported in XP3BR fibroblasts [12] from complementation Group G. In XP2LE from complementation Group C, both lymphocytes [13] and fibroblasts [14] were reported to be hypersensitive to the induction of chromosome damage and defective in the repair of single-strand breaks following {gamma}-irradiation. In these cases, there was no evidence that the patients ever underwent radiotherapy. Enhanced numbers of ionizing radiation-induced chromosome aberrations have also been reported in other fibroblast cell lines from XP complementation Group C [15], suggesting that this group may be of some significance.

We have detailed an XP patient from complementation Group C, XP14BR, with clear clinical and cellular ionizing radiation sensitivity [2], although this could be dissociated from UV sensitivity [3]. Most other evidence for the existence of hypersensitivity of XP patients at the clinical level to agents other than UV is anecdotal. M Zghal (personal communication) has suggested significant sensitivity to ionizing radiation and the radiomimetic agent bleomycin amongst XP patients in Tunisia. On the basis of these claims, radiotherapy and chemotherapy dose levels were reduced to 50% of those employed for normal individuals. Following their experiences when treating two siblings with XP of unknown complementation group, Kim et al [16] advocated caution when considering radiation therapy; a similar position was adopted by Sakata et al [17]. Di Giovanna et al [18] reported the uneventful radiotherapy of three XP patients, including one from complementation Group C with an inoperable spinal cord astrocytoma. In agreement, we show here that the fibroblast cell line XP23BE was normal in its response ([3], also this paper). In a second example from XP complementation Group C, Giglia et al [19] described a patient who died 3 months after combined radiotherapy and chemotherapy for a thalamic glioma, thus raising the possibility of hypersensitivity to the radiation, the chemotherapeutic agents or the combined treatments. We have shown subsequently that the fibroblast cell line from this patient (XP233VA) was not radiosensitive ([3], also this paper).

Cockayne syndrome (CS) is a second photosensitive condition with evidence of cellular ionizing radiation sensitivity [20]. Although the patients are sun-sensitive and defective in DNA repair, they do not show increased susceptibility to skin or other cancers [1, 21]. Again, several complementation groups have been identified [22]. CS cells are specifically defective in the preferential repair of damage in the transcribed strands of active genes — a branch of repair designated transcription-coupled repair [21]. Thus, there is a clear defect in NER in CS, but the situation is less clear with respect to the processes of base excision and single-strand break repair (e.g. [23]). Slight sensitivity to ionizing radiation and deficient repair of oxidative damage may be associated with both the major CS complementation groups [24–26].

In this paper, we examine our survival data accumulated over a 25-year period and report on the radiosensitivity of non-transformed fibroblast cultures from 33 patients with XP. We also report on fibroblast cultures from seven CS patients, and four patients with a combined XP/CS phenotype. For comparison, we present data from 8 ataxia-telangiectasia (A-T) and 53 normal fibroblast cultures. "Normal cells" comprised controls from various studies and cultures from population surveys in which no indication of radiosensitivity was found [27].


   Methods and materials
Top
 Abstract
 Introduction
 Methods and materials
Results
 Discussion
 References
 
Cells
Details of the origin of the 33 XP, 7 CS, 4 XP/CS and 8 A-T primary human fibroblast cell strains used in this investigation are given in Table 1Go. Details of the 53 normal cell strains are given in Table 2Go. Biopsies were taken in accordance with the ethical procedures in place in the institution at the relevant time.


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  		Table 1. The provenance of the xeroderma pigmentosum(XP), XP with Cockayne syndrome (XP/CS), CS and ataxia-telangiectasia (A-T) fibroblast cell lines

 

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  		Table 2. The provenance of the normal cell lines employed in this study: classification by originator of the material

 
Cell culture and irradiation
Cell culture methods have been described in detail previously [28]. All of the cells were maintained in culture using standard materials and procedures, and were verified to be free of mycoplasma infection.

Irradiation was with a 60Co source, whose dose rate decreased from ~5 Gy min–1 to 1 Gy min–1 over the period of the experiments. More detailed statistical analysis suggests that the decline in dose rate was associated with a significant increase in radioresistance (Green et al, personal communication). However, re-analysis with an allowance for dose rate gave a similar order of radiosensitivities. The experimental design followed the protocols for clonal survival as described by Arlett et al [29].

Data handling
Each plate count for each survival curve was transcribed on to a computer. Exact {gamma}-irradiation doses were computed from the length of irradiation and the calculated 60Co decay up to the date of the experiment. The general linear modelling programme GLIM (NAG, Oxford, UK) was used for subsequent calculations.

Survival curves were fitted using a "linear quadratic" model:


Formula 001

where S is the surviving fraction, D is the radiation dose in Gy, {alpha} is the linear term of the survival curve, β is the quadratic, and c is the zero dose term. An upper limit of zero was placed on β to prevent biologically unrealistic fits. From the best fit curves, various parameters for describing radiosensitivity were obtained; in a related paper (Green et al, personal communication), we evaluate these parameters. Here, we have chosen the estimate of D10 survival as a descriptive parameter of radiosensitivity that gives good discrimination between fibroblast lines. Use of D37, mean inactivation dose, or 2 Gy survival gave a closely similar order of radiosensitivities (Green et al, personal communication). Copies of the tabulation of the relevant parameters for each strain are available from the authors.


   Results
Top
 Abstract
 Introduction
 Methods and materials
 Results
Discussion
 References
 
Figure 1Go shows a cumulative frequency plot of the D10 survival estimates for 33 XP, 7 CS, 4 combined XP/CS, 8 A-T and 53 normal fibroblast lines. There is no clear evidence for a general tendency towards ionizing radiation sensitivity in the population of 33 XP fibroblasts. The same appears true for the four XP/CS fibroblast lines. As expected, the eight A-T fibroblast lines are extremely radiosensitive. The 7 CS lines appear to be slightly more sensitive as a group than the 53 normal lines.


Figure 1
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  		Figure 1. Cumulative frequency plots of the types of strain used in this investigation. The percentage of strains with 5 Gy survival below a given value is plotted. , normal strains; , xeroderma pigmentosum; , Cockayne syndrome;, combined xeroderma and Cockayne syndrome;, ataxia-telangiectasia.

 
The histograms in Figure 2Go (XP, CS and A-T lines) and Figure 3Go ("normal" controls) show the radiosensitivity of each individual fibroblast line. It can be seen that the lines derived from the two separate isolations of XP14BR are clearly more sensitive to ionizing radiation than any other XP line, and are as sensitive as an A-T "classic" (AT2BR) and variant (AT6BR) cell line [30, 31]. Among the XP cell lines, the previously reported ionizing radiation sensitivity of XP3BR [12] can be seen, but in two experiments the reported cytological or DNA repair radiosensitivity of XP2LE [32] is not confirmed by our cell survival assay. The next most sensitive XP lines were XPJCLO (complementation Group D) and XP16. This latter was obtained as a fibroblast line from JB Little (Harvard) in 1980, but we have been unable to obtain further information on the patient.


Figure 2
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  		Figure 2. D10 values for XP ({blacksquare}), CS ({square}), XP/CS ({blacksquare}) and AT ( ) strains used in this investigation. (The number of standard protocol survival curves that were performed is given in brackets.)

 

Figure 3
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  		Figure 3. D10 values for normal fibroblast strains used in this study. (The number of standard protocol survival curves that were performed is given in brackets.)

 

   Discussion
Top
 Abstract
 Introduction
 Methods and materials
 Results
 Discussion
References
 
As a group, XP fibroblasts do not appear to be more sensitive than normal cells. The mean value of D10 for the sample of "normals" is 3.34±0.41 Gy. The equivalent mean D10 for the 37 XP and XP/CS lines is 3.39±0.64 Gy. Two "normal" lines (153BR and 145BR) would appear to be more than 1.96 standard deviations more sensitive than the mean, and one (MRC5) is more resistant. Of the XP lines, only XP14BR [3] is clearly outside this range of normal sensitivity, and two lines (XP3BR [12] and XPJCLO) are borderline. However, four XP, four CS and one XP/CS line are more sensitive than all, apart from the two most sensitive normal lines uncovered in our study. The remaining cell lines do not appear to show any abnormal radiosensitivity and, perhaps surprisingly, three XP lines (XPTA-3, XP106LO and XP34BR) appear to be above the range of normal radioresistance.

It is of interest that the proportion of "normals" (2 out of 53) that might be considered to show cellular radiosensitivity is close to the proportion of "over reactors" that might be encountered in the normal population at radiotherapy [33]. The slight excess of radiosensitive XP lines may well be chance, but it could equally be that a subgroup of XP lines does react adversely to radiotherapy. Using gene transfer techniques, we have already shown that the increased radiosensitivity in XP14BR is not a consequence of a defect in the XPC gene but of the presence of a possibly novel radiosensitivity gene [3]. Thus, after the exclusion of the two derivatives of XP14BR and given the sample sizes, the proportion of "radiosensitives" are probably similar among normal and XP lines. To our knowledge, with the exception of the patient who gave rise to fibroblast culture XP14BR, the patients who generated cultures XP3BR (who is now deceased at the age of 21 years), XP16 and XPJCLO have never undergone radiotherapy and so there is no way of knowing if cellular radiosensitivity might predict clinical sensitivity in these cases.

The preponderance of CS cultures towards the sensitive end of the range confirms the reports of Deschavanne et al [20] and D'Errico et al [26]. The four cases of combined XP/CS reveal one example — XPCS2LV from XP complementation Group G — of possible hypersensitivity. However, the sibling [34] XPCS1LV is clearly not sensitive; neither was XPCS1BA nor XPCS2BA, which also represent a pair of siblings [35].

In the absence of evidence of an excess of radiosensitivity amongst fibroblasts from a panel of XP patients, how relevant are the earlier suspicions of clinical radiosensitivity? The existence of such suspicions should suggest caution when such patients receive radiation treatments. It is possible that clinical radiosensitivity of some XP patients might not be the result of deficient repair of ionizing radiation damage, and therefore may not be revealed in cellular assays. It could instead be a side-effect of lifetime exposure to UV and agents inducing bulky DNA adducts. This will have led to increased cell killing and cell turnover, and to reduced replicative potential of light-exposed tissue. It would certainly be the case that the European patients examined early in the 20th century would not have received the level of protection against solar irradiation that we would now expect. Even at an early age, patients in North Africa would necessarily experience substantial exposure. Thus, specific tissues of XP patients might be considered the equivalent of those of elderly patients or diabetics, and the radiotherapy regime might need to be tailored accordingly. Such a premature ageing mechanism could conceivably lead to acute and late ionizing radiation effects in the patient, without a corresponding radiosensitive phenotype in cell culture.

*Current address: Royal Berkshire Hospital, London Road, Reading, Berkshire, RG1 5AN, UK.


   Acknowledgments
 
We are indebted to Susan Harcourt and Anne Priestley who performed the great majority of the cell killing experiments used in this paper. The work was funded in part by EC grant B16-E1042-UK.

Received for publication February 9, 2007. Revision received April 23, 2007. Accepted for publication April 26, 2007.


   References
Top
 Abstract
 Introduction
 Methods and materials
 Results
 Discussion
 References
 

  1. Arlett CF, Lehmann AR. Xeroderma pigmentosum, cockayne syndrome and trichothiodystrophy: sun sensitivity, DNA repair defects and skin cancer. In Eeles R, Ponder B, Easton DF, Horwich EA, editors. Genetic predisposition to Cancer. London, UK: Arnold; 2004: 214-31.
  2. Rogers PB, Plowman PN, Harris SJ, Arlett CF. Four radiation hypersensitivity cases and their implications for clinical radiotherapy. Radiother Oncol 2000;57:143–54.[CrossRef][Medline]
  3. Arlett CF, Plowman PN, Rogers PB, Parris CN, Abbaszadeh F, Green MHL, et al. Clinical and cellular ionizing radiation sensitivity in a patient with xeroderma pigmentosum. Br J Radiol 2006;79:510–7.[Abstract/Free Full Text]
  4. Mikhelson VM. Defective repair of {gamma}-irradiated DNA in a case of xeroderma pigmentosum. Fort Onkol 1979;4:157–70.
  5. Martenstein H, Bobowitcz A. Uber Strahlenempfindlichkeit bei xeroderma pigmentosum (untersuchungen an einem weiteren fall). Arch Dermatol Syph 1926;150:165–76.[CrossRef]
  6. Heiner L. Adatok a bor sugarerzekenysegehez xeroderma pigmentosum-nal. Orvosi Hetilap 1925;69:540–2.
  7. Ward JF. DNA damage and repair. In Glass WA, Varma MN editors. Physical and Chemical Mechanisms in Molecular Radiation Biology. New York: Plenum Press; 1991: 403–21.
  8. Tchou J, Kasai S, Shibutani S, Chung M-H, Laval J, Grollman AP, et al. 8-oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity. Proc Natl Acad Sci USA 1991;88:4690–4.[Abstract/Free Full Text]
  9. Wood RD. Nucleotide excision repair in mammalian cells. J Biol Chem 1997;272:23465–8.[Free Full Text]
  10. Masutani C, Kusumoto R, Yamada A, Dohmae N, Yokoi M, Yuasa M, et al. The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta. Nature 1999;399:700–4.[CrossRef][Medline]
  11. Lehmann AR. Replication of damaged DNA by translesion synthesis in human cells. FEBS Lett 2005;579:873–6.[CrossRef][Medline]
  12. Arlett CF, Harcourt SA, Lehmann AR, Stevens S, Ferguson-Smith MA, Morley WN. Studies on a new case of xeroderma pigmentosum (XP3BR) from complementation group G with cellular sensitivity to ionizing radiation. Carcinogenesis 1980;1:745–51.[Abstract/Free Full Text]
  13. Mikhelson VM, Aikazian EV, Genter EI, Pleskach NM. Increased sensitivity of human cells to ionizing radiation in one of the forms of the hereditary disease xeroderma pigmentosum (a study of single-stranded DNA breaks and chromosomal aberrations). Tsitologiia 1974;16:203–10.[Medline]
  14. Mikhelson VM, Pleskach NM, Prokofeva VV. Occurrence and elimination of single- and double-strand DNA breaks in the fibroblasts of xeroderma pigmentosum patients exposed to gamma radiation. Tsitologiia 1985;27:592–8.[Medline]
  15. Price FM, Parshad R, Tarone RE, Sanford KK. Radiation-induced chromatid aberrations in Cockayne syndrome and xeroderma pigmentosum group C fibroblasts in relation to cancer predisposition. Cancer Genet Cytogenet 1991;57:1–10.[CrossRef][Medline]
  16. Kim R, Brascho DJ, Lawson AJ. Xeroderma pigmentosum in radiation oncology practice. Int J Radiat Oncol Biol Phys 1982;8:313–4.[Medline]
  17. Sakata K, Aoki Y, Kumakura Y, Karasawa K, Nakagawa K, Muta N, et al. Radiation therapy for patients with xeroderma pigmentosum. Radiat Med 1996;14:87–90.[Medline]
  18. Di Giovanna JJ, Patronas N, Katz D, Abangan D, Kraemer KH. Xeroderma pigmentosum: spinal cord astrocytoma with 9 year survival after radiation and isotretinoin therapy. J Cutan Med Surg 1998;2:153–8.[Medline]
  19. Giglia G, Bouffet E, Jouvet A, Ohgaki H, Kleihues P, Sarasin A. Molecular analysis of glioma and skin-tumour alterations in a xeroderma-pigmentsum child. Int J Cancer 1999;81:345–50.[CrossRef][Medline]
  20. Deschavanne PJ, Chavaudra N, Fertil B, Malaise EP. Abnormal sensitivity of some Cockayne's syndrome cell strains to UV- and gamma-rays. Association with a reduced ability to repair potentially lethal damage. Mutat Res 1984;131:61–70.[Medline]
  21. Lehmann AR. DNA repair-deficient diseases, xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Biochimie 2003;85:1101–11.[Medline]
  22. Stefanini M, Fawcett H, Botta E, Nardo T, Lehmann AR. Genetic analysis of twenty-two patients with Cockayne syndrome. Hum Genet 1996;97:418–23.[Medline]
  23. Mellon I. Transcription-coupled repair: A complex affair. Mutat Res 2005;577:155–61.[Medline]
  24. de Waard H, de Wit J, Andressoo JO, van Oostrom CT, Riis B, Weimann A, et al. Different effects of CSA and CSB deficiency on sensitivity to oxidative DNA damage. Mol Cell Biol 2004;24:7941–8.[Abstract/Free Full Text]
  25. Tuo J, Muftuoglu M, Chen C, Jaruga P, Selzer RR, Brosh RM, et al. The Cockayne Syndrome group B gene product is involved in general genome base excision repair of 8-hydroxyguanine in DNA. J Biol Chem 2001;276:45772–9.[Abstract/Free Full Text]
  26. D'Errico M, Parlanti E, Teson M, Degan P, Lemma T, Calcagnile A, et al. The role of CSA in the response to oxidative DNA damage in human cells. Oncogene 2007;26:4336–43.[CrossRef][Medline]
  27. Green MHL, Arlett CF, Cole J, Harcourt SA, Priestley A, Waugh APW, et al. Comparative human cellular radiosensitivity: III. Gamma-radiation survival of cultured skin fibroblasts and resting T-lymphocytes from the peripheral blood of the same individual. Int J Radiat Biol 1991;59:749–65.[Medline]
  28. Arlett CF, Harcourt SA. Survey of radio -sensitivity in a variety of human cell strains. Cancer Res 1980;40:926–32.[Abstract/Free Full Text]
  29. Arlett CF, Green MHL, Priestley A, Harcourt SA, Mayne LV. Comparative human cellular radiosensitivity: I. The effect of SV40 immortalisation on the gamma-irradiation survival of skin derived fibroblasts from normal individuals and from ataxia-telangiectasia patients and heterozygotes. Int J Radiat Biol 1988;54:911–28.[Medline]
  30. Stankovic T, Kidd AMJ, Sutcliffe A, McGuire GM, Robinson P, Weber P, et al. ATM mutations and phenotypes in ataxia-telangiectasia families in the British Isles: expression of mutant ATM and the risk of leukemia, lymphoma, and breast cancer. Am J Hum Genet 1998;62:334–45.[CrossRef][Medline]
  31. McConville CM, Stankovic T, Byrd PJ, McGuire G, Yao Q-Y, Lennox GG, et al. Mutations associated with variant phenotypes in ataxia telangeictasia. Am J Hum Genet 1996;59:320–30.[Medline]
  32. Barenfeld LS, Pleskach NM, Bildin VN, Prokofjeva VV, Mikhelson VM. Radioresistant DNA synthesis in cells of patients showing increased chromosomal sensitivity to ionizing radiation. Mutat Res 1986;165:159–64.[Medline]
  33. Arlett CF. Human cellular radiosensitivity — the search for the holy grail or a poisoned chalice. Adv Radiat Biol 1992;16:273–92.
  34. Jaeken J, Klocker H, Schwaiger H, Bellmann R, Hirschkauffmann M, Schweiger M. Clinical and biochemical-studies in three patients with severe early infantile Cockayne syndrome. Hum Genet 1989;83:339–46.[CrossRef][Medline]
  35. Vermeulen W, Scott RJ, Rodgers S, Muller HJ, Cole J, Arlett CF, et al. Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3. Am J Hum Genet 1994;54:191–200.[Medline]
  36. Lalle P, Nouspikel T, Constantinou A, Thorel F, Clarkson SG. The founding members of xeroderma pigmentosum group G produce XPG protein with severely impaired endonuclease activity. J Invest Dermatol 2002;118:344–51.[CrossRef][Medline]
  37. Taylor EM, Broughton BC, Botta E, Stefanini M, Sarasin A, Jaspers NGJ, et al. Xeroderma pigmentosum and trichothiodystrophy are associated with different mutations in the XPD (ERCC2) repair/transcription gene. Proc Natl Acad Sci USA 1997;94:8658–63.[Abstract/Free Full Text]
  38. Chavanne F, Broughton BC, Pietra D, Nardo T, Browitt A, Lehmann AR, et al. Mutations in the XPC gene in families with xeroderma pigmentosum and consequences at the cell, protein, and transcript levels. Cancer Res 2000;60:1974–82.[Abstract/Free Full Text]
  39. Broughton BC, Thompson AF, Harcourt SA, Vermeulen W, Hoeijmakers JHJ, Botta E, et al. Molecular and cellular analysis of the DNA-repair defect in a patient in Xeroderma-pigmentosum complementation Group-D who has the clinical-features of Xeroderma-pigmentosum and Cockayne-syndrome. Am J Hum Genet 1995;56:167–74.[Medline]
  40. Broughton BC, Cordonnier A, Kleijer WJ, Jaspers NGJ, Fawcett H, Raams A, et al. Molecular analysis of mutations in DNA polymerase eta in xeroderma pigmentosum-variant patients. Proc Natl Acad Sci USA 2002;99:815–20.[Abstract/Free Full Text]
  41. States JC, McDuffie ER, Myrand SP, McDowell M, Cleaver JE. Distribution of mutations in the human xeroderma pigmentosum group A gene and their relationships to the functional regions of the DNA damage recognition protein. Hum Mutat 1998;12:103–13.[CrossRef][Medline]
  42. Pawsey SA, Magnus IA, Ramsay CA, Benson PF, Giannelli F. Clinical, genetic and DNA repair studies on a consecutive series of patients with xeroderma pigmentosum. Quart J Medicine 1979;190:179–210.
  43. Nouspikel T, Clarkson SG. Mutations that disable the DNA-repair gene XPG in a Xeroderma-pigmentosum group-G patient. Hum Mol Genet 1994;3:963–7.[Abstract/Free Full Text]
  44. Petit-Frère C, Capulas E, Lowe JE, Koulu L, Marttila RJ, Jaspers NGJ, et al. Ultraviolet-B-induced apoptosis and cytokine release in xeroderma pigmentosum keratinocytes. J Invest Dermatol 2000;115:687–93.[CrossRef][Medline]
  45. Nouspikel T, Lalle P, Leadon SA, Cooper PK, Clarkson SG. A common mutational pattern in Cockayne syndrome patients from xeroderma pigmentosum group G: implications for a second XPG function. Proc Natl Acad Sci USA 1997;94:3116–21.[Abstract/Free Full Text]
  46. Troelstra C, van Gool A, de Wit J, Vermeulen W, Bootsma D, Hoeijmakers JHJ. ERCC6, a member of a subfamily of putative helicases, is involved in Cockayne's syndrome and preferential repair of active genes. Cell 1992;71:939–53.[CrossRef][Medline]
  47. Lehmann AR. Three complementation groups in Cockayne syndrome. Mutat Res 1982;106:347–56.[CrossRef][Medline]
  48. Mallery DL, Tanganelli B, Colella S, Steingrimsdottir H, Van Gool AJ, Troelstra C, et al. Molecular analysis of mutations in the CSB(ERCC6) gene in patients with Cockayne syndrome. Am J Hum Genet 1998;62:77–85.[CrossRef][Medline]
  49. Huschtscha LI, Holliday R. Limited and unlimited growth of SV40-transformed cells from human diploid MRC-5 fibroblasts. J Cell Sci 1983;63:77–99.[Abstract]
  50. Jacobs JP, Jones CM, Baillie JP. Characteristics of a human diploid cell designated MRC-5. Nature 1970;227:168–70.[CrossRef][Medline]




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