title: Clinical and cellular ionizing radiation sensitivity in a patient with xeroderma pigmentosum.
abstract: XP14BR is a cell line derived from a xeroderma pigmentosum (XP) patient from complementation group C. The patient was unusual in presenting with an angiosarcoma of the scalp, treated by surgical excision and radiotherapy. Following 38 Gy in 19 fractions with 6 MEV electrons, a severe desquamation and necrosis of the underlying bone ensued, and death followed 4 years later. The cell line was correspondingly hypersensitive to the lethal effects of gamma irradiation. We had previously shown that this sensitivity could be discriminated from that seen in ataxia-telangiectasia (A-T). The cellular response to ultraviolet radiation below 280 nm (UVC) was characteristic of XP cells, indicating the second instance, in our experience, of dual cellular UVC and ionizing radiation hypersensitivity in XP. We then set out to evaluate any defects in repair of ionizing radiation damage and to verify any direct contribution of the XPC gene. The cells were defective in repair of a fraction of double strand breaks, with a pattern reminiscent of A-T. The cell line was immortalized with the vector pSV3neo and the XPC cDNA transfected in to correct the defect. The progeny derived from this transfection showed the presence of the XPC gene product, as measured by immunoblotting. A considerable restoration of normal UVC, but not ionizing radiation, sensitivity was observed amongst the clones. This differential correction of cellular sensitivity is strong evidence for the presence of a defective radiosensitivity gene, distinct from XPC, which is responsible for the clinical hypersensitivity to ionizing radiation. It is important to resolve how widespread ionizing radiation sensitivity is amongst XP patients.
authors.affiliation: Genome Damage & Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ.
authors.forename: C F
authors.initials: CF
authors.lastname: Arlett
authors.forename: P N
authors.initials: PN
authors.lastname: Plowman
authors.forename: P B
authors.initials: PB
authors.lastname: Rogers
authors.forename: C N
authors.initials: CN
authors.lastname: Parris
authors.forename: F
authors.initials: F
authors.lastname: Abbaszadeh
authors.forename: M H L
authors.initials: MH
authors.lastname: Green
authors.forename: T J
authors.initials: TJ
authors.lastname: McMillan
authors.forename: C
authors.initials: C
authors.lastname: Bush
authors.forename: N
authors.initials: N
authors.lastname: Foray
authors.forename: A R
authors.initials: AR
authors.lastname: Lehmann
mesh_terms: D016923:Cell Death / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics; D005720:Gamma Rays / Q000009:adverse effects; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006394:Hemangiosarcoma / Q000532:radiotherapy*; D006801:Humans; D010020:Osteonecrosis / Q000209:etiology; D010294:Parietal Bone / Q000473:pathology / Q000528:radiation effects; D011832:Radiation Injuries / Q000235:genetics / Q000473:pathology; D011836:Radiation Tolerance / Q000235:genetics*; D012535:Scalp; D012878:Skin Neoplasms / Q000532:radiotherapy*; D014162:Transfection; D014466:Ultraviolet Rays / Q000009:adverse effects; D014983:Xeroderma Pigmentosum / Q000150:complications* / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C086984:XPC protein, human