title: Use of tissue culture models to study environmental-genetic interactions relevant to neurodegenerative diseases.
abstract: 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.
authors.affiliation: Montreal Neurological Institute, McGill University, Quebec, Canada.
authors.forename: H D
authors.initials: HD
authors.lastname: Durham
authors.forename: C
authors.initials: C
authors.lastname: O'Brien
authors.forename: J
authors.initials: J
authors.lastname: Nalbantoglu
authors.forename: D A
authors.initials: DA
authors.lastname: Figlewicz
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D002891:Chromosomes, Human, Pair 21 / Q000187:drug effects; D002999:Clone Cells; D046508:Culture Techniques; D004852:Epoxy Compounds / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000166:cytology*; D009498:Neurotoxins / Q000633:toxicity*; D010084:Oxidation-Reduction; D016716:PC12 Cells / Q000187:drug effects; D051381:Rats; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D004852:Epoxy Compounds; D009498:Neurotoxins; C013690:styrene oxide; D013482:Superoxide Dismutase