Chemistry professor Dr. Bill Luttrell, with the help of OC science students, conducts research every summer. Below is an overview of his primary research interests:
Effects of Environmental and Workplace Chemical Exposures on Drug Metabolizing Enzyme Systems in the Liver—Implications for Chemical-Drug Interactions in People
Exposure to toxic chemicals in the workplace or environment can alter the way the body responds to the administration of therapeutic drugs, other xenobiotics (foreign materials), and endogenous materials. My area of research interests has focused on the effects of environmental and workplace chemical exposures on drug metabolizing enzyme systems in the liver. I am particularly interested in identifying chemical-drug interactions that may occur in exposed worker populations and the implications this might have on the use of therapeutic drugs in this group of people. In the past, I have studied the effects of organophosphate compounds on drug metabolizing enzymes in the livers of guinea pigs, rats, and mice by pretreating them with compounds such as soman or paraoxon and then performing assays for measuring the liver microsomal enzyme activities of carboxylesterase, aniline hydroxylase, and procaine esterase. Sufficient data was collected to perform Michaelis-Menten enzyme kinetic studies using Lineweaver-Burk plots. One of the findings of these initial studies was that a metabolite of soman, 3,3-dimethyl-2-butanone (pinacolone), was involved in the enzyme enhancement caused by soman pretreatment in guinea pigs. Studies in the literature have also shown that other ketones, such as acetone, can produce liver microsomal enzyme enhancement. Currently, I am studying the effects of a series of ketone compounds on these three enzyme systems in liver microsomes of mice. In order to determine if the molecular weight or size of the ketone metabolite influences degree of enzyme enhancement, five ketones of increasing molecular weight or size (acetone, 2-butanone, 2-pentanone, 2-hexanone, and 3,3-dimethyl-2-butanone) were selected for pretreating mice. Studies with these five ketones have been completed using the carboxylesterase and aniline hydroxylase assays. Currently, I am conducting studies using the procaine esterase assay. My hope is to identify and evaluate chemical-drug interactions in people and learn whether this can result in adverse effects or loss of therapeutic effects of commonly used prescription drugs. With this information we can then better inform workers and people in the general population of the risks of exposure to toxic chemicals.
Research student recording data on the flame atomic absorption spectrophotometer.