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will enable physicians to identify adverse effects from drugs used to treat HIV/
AIDS, hepatitis, and other infectious diseases. Several assays for detection of
molecular toxicology are commercially available.
Gene Expression Studies
Gene expression is used widely to assess the response of cells to various substances.
Two technologies will be described to illustrate the use in molecular toxicology
studies.
DNA Microarrays These allow the monitoring of the expression levels of thou-
sands of genes simultaneously and can be used as a highly sensitive and informative
method for toxicogenomics. Transcript profi ling technology has been used to pre-
dict adverse toxicity for novel or untested compounds. cDNA microarray platforms
have been designed specifi cally for gene expression events of relevance to a large
number of toxicological endpoints. Such arrays allow comprehensive coverage of
genes associated with entire pathways (such as oxidative stress, signal transduction,
stress response, epithelial biology) and enable simultaneous measurement of more
several thousand gene expression events.
Ames Mutagenicity Assays (Xenometrix) The Ames MPF and Ames II assays are
modifi ed versions of the Ames test using liquid culture instead of agar plates.
Advantages of this format are the lower amount of sample needed and much easier
handling.
Cytotoxicity assays were among the fi rst in vitro bioassay methods used to
predict toxicity of drugs to various tissues. Xenometrix offers a broad range of cyto-
toxicity assays for the in vitro evaluation of cells in response to pharmaceutical or
chemical compounds. They are based on well established, sensitive and reliable
endpoints of cytotoxicity and growth inhibition and are adapted for high throughput
in microtiter plates.
Pharmacogenetics in Clinical Trials
Currently, the most signifi cant polymorphisms in causing genetic differences in
phase I drug metabolism are known and therapeutic failures or adverse drug reac-
tions caused by polymorphic genes can be predicted for several drugs. Further
investigations need to be done on the consequences of each pharmacogenetic phe-
nomenon. Pharmacokinetic or pharmacodynamic changes my determine drug selec-
tion or dose adjustment. This information can be used by the pharmaceutical
industry for drug development.
Patients are being genotyped in clinical trials. Application of benefi t of this
approach in needs to be verifi ed in prospective clinical trials using the parameters of
4 Pharmacogenetics