Toxicity cellular assays

Profiling environmental chemicals by a defined set of biochemical and cellular assays raises important concerns about the means by which this information can be used to predict in vivo developmental toxicity and in broader terms the use of this HTS information for problem formulation steps in a lifestage-specific risk assessment. 

A fraction of our in-house -8500 ATP-site competitor compounds have been profiled in a number of cellular assays for toxicity, solubility, and permeability. Nontoxic, soluble, permeable compounds have been gathered into a subset of the main library, which we call the validation library . The validation library currently... 

Ekwall, B, Bondesson, 1, Catell, J.V., Gomez-Lechon, M. J., Heiberg, S., Hogberg, J. Jover, R., Ponsoda, X., Rommert, L., Stenberg, KL., Walum, E. (1989) Cytoxocity evaluation of the first ten MEIC chemicals Acute lethal toxicity in man predicted by cytotoxicity in five cellular assays and by oral LD50 tests in rodents. ATLA 17 83-100. 

Cysteamine (HSCH2CH2NH2) has been found to add to Michael acceptors, such as thujone, in dimethylsulfoxide (DMSO). By contrast, no reaction occurred in nonpolar solvents. NMR spectroscopy was employed to identify good Michael acceptors and sort them into reversible and irreversible thiol sinks with a view of developing a cellular assay for thiol-trapping agents. In another paper, calculated transition-state energies of the reaction of Michael acceptors with MeSH have been used as model system to asses thiol toxicity in aqueous media. ... 

Examples of biomarker assays operating at different levels are given in Table 4.2. The recent development of omics technology should provide strong support to this approach (Box 4.3). Microarray analysis, for instance, can give a time-related sequence of gene responses that relate to the cellular changes of toxicity. 

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