The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 1996-1997

Cellular-based Assays to Detect Toxic Agents and Elucidate the Underlying Genetic and Biochemical Mechanisms of Toxicity

Michael Scott Dubow, PhD
McGill University, Montreal, Quebec

The basis of this research is the principle that cells will augment or repress the expression of specific genes, upon exposure to bioavailable doses of a toxic agent, in order to re-orient cell physiology to cope with the stress. To identify and quantitate the activity of these genes, the investigators have prepared a "library" of luciferase gene fusions in the bacterium E. coli and have identified a number of clones whose luminescence changes upon cellular exposure to a variety of compounds. These clones are being validated for use as luminescent "biosensors" to detect toxic agents. Dubow and colleagues will now focus on bacterial clones which are induced by the anti-oxidants selenium and DMSO, and the pesticides bromacil, chlordane, dinoseb, and the plastic stabilizer tributyltin. These and related studies will be used to develop molecular probes (and ultimately antibodies) for cellular-based assays for toxicity and safety evaluation.