UC Toxics News: Fall 2006
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TSR&TP Trainee Nature McGinn studies the effects of pharmaceutical pollution on invertebrate development.

When we swallow a pill, some of the drug is excreted as waste and travels from our sewage systems to rivers and oceans. Traces of birth control, pain relievers, antidepressants and other drugs have been detected in our drinking water.

These levels of pharmaceuticals aren’t toxic, but are they harmful?

Nature McGinn, a doctoral student in Physiology at UC Davis, received a TSR&TP fellowship to study the effects of some pharmaceuticals on the development of marine mussels.

While searching for her thesis topic, McGinn was inspired by a website detailing the problem with pharmaceuticals and personal care products in the environment by Christian Daughton, an EPA scientist. There is evidence that pharmaceuticals found in the environment may be implicated in multidrug resistance in humans, the process by which cancer cells become resistant to multiple therapeutic drugs. In animals, this is called multixenobiotic resistance (MXR), a cellular defense mechanism against pollutants. “I had an immediate connection with tying pharmaceuticals and MXR,” says McGinn.

The MXR system is the general chemical defense system in aquatic animals. It is a membrane based active transport system that pumps toxicants from inside cells. It prevents intracellular accumulation of toxics and allows cells to function normally in the presence of pollutants.

Previous research conducted at the Bodega Marine Laboratory and other institutions established a link between synthetic musks, artificial fragrances found in lotions, detergents and other personal care products, and interference of MXR. McGinn decided to expand on this research to pharmaceuticals. She chose to look at ibuprofen and fluoxetine (Prozac) because they are found in the environment in quantities high enough to have an effect. MXR is a vital system, especially in marine invertebrates. “Inhibition of this transport system might make organisms vulnerable to a range of toxic chemicals,” explains McGinn.

Dye accumulation assay of multixenobiotic resistance function: The 2-cell embryos in Figure A were incubated with the calcein-AM dye, an MXR transport protein substrate, while the embryos in Figure B were incubated with calcein-AM plus an MXR transport inhibitor. In B, where the transport proteins that would normally carry the dye out of the cells are inhibited, the calcein-AM is trapped within the cell where it is cleaved into its fluorescent form, calcein.

MXR in marine organisms and human resistance to chemotherapeutic drugs are mediated by the same protein, P-glycoprotein. McGinn has been working on producing a P-gp antibody that will react with the mussel cells to show expression of MXR proteins during their development. Using a fluorescent dye that would normally be pumped out of the cells by MXR proteins, she can get a quantitative analysis of their level of activity in the presence of specific inhibitors. “My final goal,” says McGinn, “will be to have a clear idea about how these pharmaceuticals interact with MXR in developing mussels.”

“Having a TSR&TP fellowship has been a great experience”, says McGinn. “It has helped me understand what’s going on everywhere else, especially in the UC system. The funding has allowed me to do things I wouldn’t have been able to like going to Canada and taking an intensive course on molecular biology techniques and doing PCR and mRNA analysis that is quite expensive. It will allow me to round things out with the characterization of MXR in mussels, protein expression, protein function and gene expression.”


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