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Genes identified that protect against heart damage from chemotherapy
Date:12/3/2007

imple yeast cells from Dr. Anil Cashikars yeast knockout collection. Yeast, which have about 6,000 genes compared to humans 30,000, are good models for study of human cells because they include the same basic cellular functions such as replication, DNA repair, signaling and even cell death, says Dr. Cashikar, MCG geneticist and a study co-author.

They found 71 genes that conveyed varying degree of protection from doxorubicin. The cell does not have a unique mechanism to protect from doxorubicin; its a very complex response, says Dr. Flores-Rozas. Some genes protect better than others. But in the absence of some of these genes, the cells will die from exposure to the drug.

The genes may even protect cancer and cardiac cells differently, he says noting one way doxorubicin stops cancer cells is by preventing their classic rapid division. Cardiac cells, on the other hand, dont divide. Still theres some common ground between the cells when it comes to protection. Cardiac cells have been known to use heat shock proteins to protect themselves from toxic injuries. This enables proteins made by cells to continue to function properly. If you have activated heat shock response, you have more activate proteins, says Dr. Flores-Rozas. If you have proteins that dont function, the cell is eventually going to die. The MCG researchers have shown the heat shock response also is activated in a stressed cancer cell.

He notes these newly identified protective genes likely already are expressed at some level before the cells are confronted with a stress such as a chemotherapeutic agent, then step up expression in response. If it doesnt, doxorubicin will kill them, Dr. Flores-Rozas says.

The MCG researchers suspect the genes may be protective from other stresses, such as a viral infection, as well.

They already are looking at their function and expression in cancer and cardiac cells normally and when exposed to doxorubicin.


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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia  
Source:Eurekalert

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