Hypersensitivity of ataxia-telangiectasia fibroblasts to a nitric oxide donor.


Journal Article

Ataxia-telangiectasia (A-T) is a human autosomal recessive disease characterised by immunodeficiency, extreme sensitivity to ionising radiation and progressive cerebellar ataxia. The defective gene has recently been cloned and is a member of the phosphatidylinositol 3-kinase family. We have investigated the possibility that the neurodegeneration in A-T might be induced by an endogenously formed mutagen causing radiation-like damage. Nitric oxide is known to be formed in the cerebellum and we present evidence that A-T fibroblasts are hypersensitive to killing by the nitric oxide donor S-nitrosoglutathione (GSNO), as are fibroblasts from a radiosensitive individual without ataxia. Killing was determined as loss of colony forming ability. GSNO induces dose-dependent DNA strand breakage, but to no greater extent in A-T fibroblasts. Breakdown of GSNO to nitrite and nitrate appears to occur to the same extent in both normal and A-T fibroblasts. Cell killing by GSNO appears to be associated in both types of cell with formation of nitrite, rather than nitrate, as the ultimate oxidation product of nitric oxide.

Full Text

Cited Authors

  • Green, MH; Marcovitch, AJ; Harcourt, SA; Lowe, JE; Green, IC; Arlett, CF

Published Date

  • January 1997

Published In

Volume / Issue

  • 22 / 1-2

Start / End Page

  • 343 - 347

PubMed ID

  • 8958160

Pubmed Central ID

  • 8958160

Electronic International Standard Serial Number (EISSN)

  • 1873-4596

International Standard Serial Number (ISSN)

  • 0891-5849

Digital Object Identifier (DOI)

  • 10.1016/s0891-5849(96)00336-x


  • eng