Toxicogenomics and Toxicoproteomics
- PDF / 635,979 Bytes
- 20 Pages / 547.087 x 762.52 pts Page_size
- 104 Downloads / 180 Views
III.H.1 III.H.2 III.H.2.1 III.H.2.2 III.H.2.2.1 III.H.2.3 III.H.2.4 III.H.3 III.H.3.1 III.H.3.2
III.H.3.3 III.H.3.4 III.H.3.5 III.H.3.6
General Considerations . . . . . . . . Toxicogenomics . . . . . . . . . . . . . . . . Total RNA Isolation . . . . . . . . . . . . . Global Expression Profiling . . . . . . Affymetrix GeneChip. . . . . . . . . . . . Focused Arrays . . . . . . . . . . . . . . . . . Real-time PCR (Taqman) . . . . . . . . Toxicoproteomics. . . . . . . . . . . . . . . Extracting Proteins from Biological Samples . . . . . . . . . . . . . . Two Dimensional Gel Electrophoresis/ Mass Spectrometry (2DE/MS) . . . Mass Spectrometry (MS) . . . . . . . . Liquid Chromatography / Mass Spectrometry (LC/MS) . . . . . . . . . . Quantitative Mass Spectrometry (QMS) . . . . . . . . . . . . . . . . . . . . . . . . . . Retentate Chromatography / Mass Spectrometry (RC/MS) . . . . . . . . . .
849 850 850 851 851 853 855 858 859
860 862 864 865 866
III.H.1 General Considerations In toxicology, the full range of genomics and proteomics technologies can be used in efforts to uncover the cellular and biochemical mechanisms at work in response to xenobiotic/toxin exposures. These new technologies offer several practical benefits. Due to a parallel approach, it should be possible to screen for toxic effects more rapidly than with conventional methods, such as histopathology and clinical chemistry. Since molecular changes occur prior to pathological outcomes, detection of disease and organ toxicity should be possible at earlier time-points during a pathological process. In addition, these technologies are highly sensitive, so that long-term toxic effects can potentially be detected at lower doses. Today, genomics and proteomics applications in toxicology are mainly used for differential expression analysis (Bandara 2002; Kennedy 2002; Wetmore
Merrick 2004; Ellinger-Ziegelbauer et al. 2004; Ezendam et al. 2004) – the measurement of a gene/protein expression in two samples, comparison of corresponding expression levels and subsequent identification of differentially expressed genes/proteins. Applications can be divided into two broad and partly overlapping classes: investigative studies and predictive toxicology. Investigative studies may help to identify new molecular targets for toxicants or provide novel and deeper insights into mechanisms of action (Man et al. 2002; Ruepp et al. 2002; Fella et al. 2005; Hewitt et al. 2005). The belief that different groups or classes of compounds will induce specific molecules or expression patterns provides the basis for predictive toxicology. Such single markers or gene/protein patterns can have a high degree of predictive power (Elcombe et al. 2002; Li et al. 2002; Petricoin et al. 2002; Ellinger-Ziegelbauer et al. 2004). Currently, researchers try to set up databases with expression profiles derived from known toxins. These can in the future be used to screen novel compounds in the drug discovery and pre-clinical evaluation processes. REFERENCES Bandara LR, Kennedy S (2002) Toxicoprot
Data Loading...
