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USE OF TISSUE CULTURE MODELS TO STUDY ENVIRONMENTAL‐GENETIC INTERACTIONS RELEVANT TO NEURODEGENERATIVE DISEASES
Author(s) -
Durham Heather D.,
O'Brien Catherine,
Nalbantoglu Josephine,
Figlewicz Denise A.
Publication year - 1995
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1995.tb02019.x
Subject(s) - amyotrophic lateral sclerosis , superoxide dismutase , gene , biology , cytotoxicity , genetics , biochemistry , oxidative stress , disease , in vitro , medicine , pathology
SUMMARY 1. Clonal cell lines, primary cultured neurones and transgenic animals expressing mutant genes linked to familial forms of neurodegenerative diseases provide models in which to examine the interaction between expression of a predisposing gene and exposure to neurotoxic chemicals. Methods of establishing these models are reviewed. 2. Mutations in the gene encoding Cu/Zn‐superoxide dismutase (SOD‐1) have been identified in cases of familial amyotrophic lateral sclerosis linked to chromosome 21. We report that in clonal lines of PC12 cells, the cytotoxicity of a glutathione‐depleting epoxide, styrene oxide, varied with SOD activity in a manner similar to that previously demonstrated for redox cycling chemicals. These preliminary data suggest that either low or high SOD‐1 activities may be associated with greater toxicity of a variety of neurotoxic chemicals and their metabolites.