93% carcinogens had at least one positive result Ames relatively good spec – 73.9%, all others less than 45%, combinations even lower
75 chemical validation Prediction of carcinogenicity – sensitivity – 71%, specificity – 100%
Malathion metabolite organophosphorus pesticide Positive in SCE, MLA
Dcb = neg/neg Bis a = pos/neg Mala = pos/pos Acet = pos/pos SDDC sodium diethyldithiocarbamate
Absorb in the region used to assess cell density – 620nm red/orange (570-750) blue/green (450-570) excitation and emission are 485nm and 535nm and as such this light will be absorbed by red and yellow compounds, causing a reduction in the intensity of both signals. This is reflected in the results as negative interference – the GFP induction signal decreases as compound concentration increases. Absorbance GFP signal apparently decreases as cell density increases Colour Does not appear to be absorbing GFP signal decreases as chemical concentration increases
Yellow, red or blue pigmentation in flowers protection from microbes and insects Quercetin Quercetin is a flavonoid and more specifically a flavonol (see below), that constitutes the aglycone of the glycoside rutin . In studies, quercetin is found to be the most active of the flavonoids, and many medicinal plants owe much of their activity to their high quercetin content. Quercetin has demonstrated significant anti-inflammatory activity because of direct inhibition of several initial processes of inflammation . For example, it inhibits both the production and release of histamine and other allergic/inflammatory mediators . In addition, it exerts potent antioxidant activity and vitamin C -sparing action. Beneficial compounds of fruit, vegetables, tea and red wine
This type of receptor gets activated upon ligand binding. After a hormone binds to the corresponding receptor, the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes No GRE in GADD45a The opposite mechanism is called transrepression . The activated hormone receptor interacts with specific transcription factors and prevents the transcription of targeted genes. Glucocorticoids are able to prevent the transcription of any of immune genes, including the IL-2 gene. to prevent the acute transplant rejection and the graft-versus-host disease
by preventing deacetylation Induce up- and down-regulation of a small subset of genes Showing promise in clinical studies, decrease toxicity of current drugs and increase efficacy/delay tolerance
Kept a constant level of Arsenite (high and low concentrations) and added either 5uM or 1uM JNKi and ran assay Arsenite thought to work through JNK pathway JNK inhibitor used
Already got mutated p53 site from Paul’s phd -532M WT1 involved in p53 response TRE/AP-1 thought to be involved in activation by MAPK pathways
GFP induction is decreased with the 532M reporter and in the WI-L2-NS cell line
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