Use of oligonucleotide arrays to analyze drug toxicity.
The advent of oligonucleotide arrays allows the simultaneous analysis of the expression of thousands of genes. This powerful technology, highly dependent on advanced analysis tools, can transform the level of information currently available on the mechanisms underlying drug-related toxicity. It is now possible to analyze the global transcriptional response to a drug and determine the global pathways associated with the effects of this agent. This analysis can be performed on samples from patients that developed a toxic effect, on cells exposed to the toxic agent, and in animal models of toxicity. Especially useful is the comparison of transcriptional responses in animals susceptible to drug-induced disease with those of genetically modified animals that are resistant to this effect. This analytic strategy allows the delineation of specific mechanisms relevant and specific to drug-induced toxicity and thus might lead to novel therapeutic interventions in these toxic reactions.
Kaminski
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Lung Biology Center and Cardiovascular Research Institute, University of California, San Francisco 94143, USA. kamins@itsa.ucsf.edu
Allard
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Heller
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RA
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000633:toxicity; D001761:Bleomycin / Q000494:pharmacology / Q000633:toxicity; D004195:Disease Models, Animal; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D005355:Fibrosis / Q000139:chemically induced / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D000970:Antineoplastic Agents; D012333:RNA, Messenger; D001761:Bleomycin