Electrochemical Toxicity Sensors

Authors

James F. Rusling Department of Chemistry, University of Connecticut

Publication Date

4/13/04

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Abstract

Medical abnormalities from exposure to toxic chemicals constitute a critical public health problem in our modern world. The use of toxic chemicals in agriculture, heavy industry, and other human endeavors throughout the past century has led to widespread pollution of our environment with potential disease-causing substances. New drugs also have important toxicity issues. Twenty years ago, Singer and Grunberger estimated that 65,000 chemicals were commonly used in modern society, and over 200,000 new chemicals were discovered each year. Since that time, advances in automated methods of chemical synthesis including combinatorial techniques have led to an explosion into the millions of new chemicals produced each year for end-use applications including drugs, agriculture, personal care, and nutrition. While only a fraction of these new compounds will turn out to be acutely toxic, those that do may have long-term possibilities of causing cancer and reproductive damage.

A major mechanism of chemical toxicity involves activation of chemicals by catalytic oxidation mediated by cytochrome P450 (cyt P450) enzymes in the liver. Lipophilic molecules bioactivated in this way often damage genetic material (i.e., DNA). They include styrene, benzo[a]pyrene, napthylamines, and many others. Covalent DNA adducts of these activated molecules with DNA bases are important biomarkers of cancer risk in humans exposed to toxic molecules.

Conventional toxicity evaluation of new chemicals proceeds from microbiological testing to animal testing and is expensive and time consuming. While advances in speed and automation of microbiological test are on the horizon, simple, inexpensive chemical screening protocols that could be used at early stages of commercial consideration would be very useful. One such scheme could be based on enzyme bioactivation of the chemicals with detection of DNA damage from the resulting metabolites. Sensors built on this principle could be used to screen chemicals and metabolites that clearly damage DNA. These compounds could then be eliminated from further commercial consideration and testing. Such a screening process could decrease the cost of bringing new drugs and agricultural chemicals to the marketplace by eliminating toxic candidates early in their commercial development and lightening the burden on toxicity bioassays. Of course, new commercially viable chemicals would still need to be subjected to microbiological and animal testing before final marketing.