Cellular radiosensitivity in human severe-combined-immunodeficiency (SCID) syndromes.

Abstract

PURPOSE:

The aim of the work was to establish to what extent a variety of human severe-combined-immunodeficiency (SCID) disorders are associated with in vitro cellular hypersensitivity to ionizing radiation.

MATERIALS AND METHODS:

A study was made of fibroblast strains established from individuals with adenosine deaminase deficiency, T(-)B(-) SCID, Omenn's syndrome and a SCID heterozygote. For comparison, an assessment was also made of the radiosensitivity of a series of fibroblast strains derived from: normal donors, a patients with ataxia-telangiectasia (A-T) and an A-T heterozygote. Radiosensitivity was determined using a clonogenic assay following both high (HDR) and low (LDR) dose-rate irradiation.

RESULTS:

Following HDR irradiation, the fibroblast strains derived from the different human SCID disorders displayed a wide range of radiosensitivity: the adenosine deaminase deficiency cells were similar in radiosensitivity to normal fibroblasts, T(-)B(-) cells were as hypersensitive to radiation as A-T cells and the Omenn's syndrome cells showed intermediate radiosensitivity. However, whereas all four normal cell strains studied showed significant LDR sparing, none of the SCID fibroblasts did.

CONCLUSIONS:

These data indicate that human SCID is variable in terms of radiosensitivity depending on the particular defect. In addition, the lack of LDR sparing of radiation-induced damage suggests the involvement of some form(s) of DNA repair defect in all the human SCID syndromes.

• Authors: A R Sproston, C M West, J H Hendry
• Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (Radiother Oncol) Vol. 42 Issue 1 Pg. 53-7 (Jan 1997) ISSN: 0167-8140 [Print] Ireland
• PMID: 9132827 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adenosine Deaminase

Topics

• Adenosine Deaminase (deficiency)
• Cell Survival
• Cells, Cultured (radiation effects)
• Colony-Forming Units Assay
• Dose-Response Relationship, Radiation
• Fibroblasts (cytology, radiation effects)
• Humans
• Radiation Dosage
• Radiation Tolerance (immunology)
• Reference Values
• Severe Combined Immunodeficiency (genetics, immunology)