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

Commemorative Booklet for CAAT 20th Anniversary Symposium

In Vitro Systems To Study Transport of Lead

Desmond I. Bannon1, Matthew E. Portnoy2, Peter S.J. Lees2, Valeria C. Culotta2, and Joseph P. Bressler2
1Johns Hopkins University, Baltimore and 2Kennedy Krieger Research Institute, Baltimore

The long-term objective of our research is to define risk factors that affect an individual's susceptibility to lead poisoning. In particular, we have focused on the possible connection between poor nutrition and increased susceptibility by observing whether metal transporters in the intestine transport lead.

We have used in vitro systems in these studies as an alternative to research with live rats. A mutant strain of Sacchromyces cerevisiae showed a significant increase in the transport of lead. This strain also overexpressed the divalent metal transporter 1 (DMT1), the major iron transporter in the intestine. DMT1 is affected by the amount of iron in a person's diet; those who eat less iron-rich foods have more of the protein. We found that DMT1-dependent lead transport was H+-dependent and inhibited by iron.

More recently, we found that the transport of lead was inhibited by iron and was H+-dependent in Caco-2 cells. This cell line expresses many properties associated with the epithelial cells lining the human intestine and often is used in studies of intestinal transport.

In summary, our studies have used in vitro systems to demonstrate that the intestinal iron transporter DMT1 transports lead. Future studies will determine whether other intestinal transporters also do so.