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- Title
PI-43.
- Authors
Rieder, M. J.; Tucker, M. J.; Carter, D.; Rieder, S. W.
- Abstract
Background/aims: To identify genes differentially expressed in sulfamethoxazole (SMX)-sensitive and resistant individuals.Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 2 volunteers: one sensitive to SMX, and one not. The cells were incubated at 37°C in a humidified CO2 atmosphere for 0, 4, or 8 hours with 100μM SMX-NO, the presumed toxic nitroso-metabolite of the parent SMX. At the designated times, RNA was isolated from the cells using Trizol followed by an Rneasy column. RNA quality was analyzed by an Agilent 2100 Bioanalyzer. Each sample was biotinylated and hybridized to an Affymatrix HGU133 plus 2.0 gene chip and scanned for the expression of 38,500 well characterized human genes.Results: Initially 19 genes implicated in stress, apoptosis or immune activation were identified that are expressed five-fold higher in the control, but not in the sensitized individual. These include 5 heat shock proteins, TNF-α, apoptosis-inducing kinase, MAPKKK1, ras, CD58, and a calcium membrane channel protein.Conclusions: Study of the differential gene expression by individuals exposed to toxic drug metabolites will help us to understand the mechanisms of cell death involved in adverse drug reactions.Clinical Pharmacology & Therapeutics (2005) 79, P18–P18; doi: 10.1016/j.clpt.2005.12.064
- Subjects
GENE expression; SULFONAMIDES; METABOLITES; CELL death; APOPTOSIS
- Publication
Clinical Pharmacology & Therapeutics, 2006, Vol 79, Issue 2, pP18
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1016/j.clpt.2005.12.064