Use of tissue culture models to study environmental-genetic interactions relevant to neurodegenerative diseases.
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.
Durham
H D
HD
Montreal Neurological Institute, McGill University, Quebec, Canada.
O'Brien
C
C
Nalbantoglu
J
J
Figlewicz
D A
DA
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
D004852:Epoxy Compounds; D009498:Neurotoxins; C013690:styrene oxide; D013482:Superoxide Dismutase