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New technique helps scientists reveal interactions between genes and drugs

ed as part of the effort to map the human genome. Researchers at the Centre d'Etude du Polymorphisme Humain in Paris, France have created approximately 700 human cell lines from multiple generations of large families in Utah, France and elsewhere.

Washington University scientists exposed cells from more than 400 of the lines to varying doses of two chemotherapy drugs, 5-fluorouracil and docetaxel. The cells were non-cancerous, but chemotherapy can kill both cancerous and non-cancerous cells. Chemotherapy is given as a treatment for cancer because cancer cells are generally more sensitive to its effects, but many factors, including the genetics of the cells' non-cancerous precursors, can influence that sensitivity.

Scientists used a robotic screening system to look for cell lines with increased sensitivity to the drugs, demonstrated by higher numbers of cell deaths in response to low drug doses. The robot also highlighted cell lines with high resistance to the drugs where few or no cells were killed.

In the future, patients whose cells are particularly sensitive to chemotherapy may be able to be treated with relatively low doses, reducing side effects. Patients whose cells are particularly resistant may need special or added medications to assure a good outcome.

Scientists already know a great deal about inheritance of genetic markers among the cell lines. This enabled Washington University researchers to compare and contrast the genetics of a cell line with altered sensitivity to cell lines from other family members and from multiple generations of the same family. Children get a random mixture of genes from both parents, so both genetic markers and changes in sensitivity are sometimes passed from parent to child and sometimes aren't. When a particular genetic marker is consistently passed from parent to child at the same time as a change in sensitivity, that tells scientists they need to look near the marker for a
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Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
2-Aug-2004


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