|
Determination of the Drug Safety Profile using Cell Membrane Microarray
Gabriel Barreda, Director, IMG Pharma Biotech S L
Drug discovery departments try to develop new high throughput screening tools to improve the processes of pharmacological characterization and drug safety profiles. DNA, protein or tissue microarrays have important limitations for predicting drug toxicity, but cell membrane microarrays (CMM) are very useful for this purpose. Microarrays composed of membranes isolated from rat tissues and cells that overexpress a specific GPCR, were applied to a set of pharmacological techniques. CMM were incubated with [3H]-SR141716A, [3H]-NMS and [3H]-CGP54626 to label binding sites for cannabinoid, muscarinic and GABAergic compounds. The distribution of the receptors was also validated by immunochemical studies with specific antibodies. In addition, the pharmacological effects promoted by the drug (WIN55,212-2, carbachol or baclophen) was also evaluated using [35S]GTPgammaS assays. The results obtained with CMM are similar to those observed using conventional techniques. Moreover, the density profiles obtained in CMM with tritiated radioligands are in agreement with the response induced by agonists. Therefore, CMM allow the identification of the therapeutic and the non-desired target receptors, the organs or tissue where they are located and the effects that the analyzed molecule could induce on specific tissues or cells in a single miniaturized assay.
Genotoxicity of the Wastewater in a Lebanese University Hospital using the SOS Chromotest and the Ames Fluctuation Test
Roula Abdel-Massih, Associate Professor, University of Balamand
Laboratory activity and drug excretion into hospital wastewater may contaminate the aquatic environment and have an impact on human health. The aim of this study is to assess and quantify the genotoxic potential of Lebanese Hospital wastewater and to provide recommendations according to the results. The SOS chromotest and the Ames test were used in a preliminary screening. These tests are complementary and help widen the spectrum for genotoxic potential. The samples were taken from 5 different pits, 2 times per day in the morning and the afternoon during two 1-week periods. 50% of the samples were positive in the SOS chromotest and 75% in the Ames test. Genotoxicity of the sample was affected by the time, day, and season of sample collection. Monday samples were the most genotoxic irrespective of the sampling time or season. Different pits, representing different wastewater collection points, also varied with respect to intensity of genotoxicity. More genotoxic tests are currently underway to further evaluate the toxicity of these samples and to identify the genotoxic compounds.
|
