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Arsenic and old telomerase: Hopkins researchers unravel effects of arsenic on human cells

Researchers at Johns Hopkins report discovering a mechanism that may account for the paradoxical effects of arsenic, which is both a treatment for cancer and a carcinogen.

Once a crucial element in the medical repertoire of Hippocrates for successfully treating infections like malaria, syphilis and yaws, arsenic is also an effective treatment for certain types of leukemia, or cancer of white blood cells. Long-term exposure to arsenic in drinking water, however, has been linked to cancer of the bladder, lungs, skin, kidney, nasal passages, liver and prostate.

"Arsenic has dual effects depending on the background; in normal cells it can cause cancer, and in cancerous cells it can lead to cell death. We have found one mechanism that may explain both of these effects," says Chi V. Dang, M.D., professor and director of hematology at Hopkins and co-author of the paper.

Specifically, Dang and his team found that arsenic inhibits transcription of a gene, hTERT, that in turn inhibits the expression of telomerase, an enzyme that protects the ends of chromosomes. Low levels of telomerase cause end-to-end fusions of chromosomes, which promote genetic instability. This instability may then lead to cancer in healthy cells and apoptosis, or cell death, in cancerous cells, according to Dang.

The Hopkins researchers report their findings in the current issue of The Journal of Clinical Investigation.

Serendipity had much to do with the discovery, according to Dang. While investigating how cancer cells react to arsenic, one of the researchers, Wen-Chien Chou, a graduate student in human genetics and molecular biology at Hopkins, noticed that some of the cells were abnormally large and tended to die sooner than expected. They then found that these big cells also had end-to-end fusion of their chromosomes, suggesting that arsenic was somehow causing genetic instability.

"It didn't take long to put two and two together," says Dang.
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Contact: Trent Stockton
tstockt1@jhmi.edu
410-955-8665
Johns Hopkins Medical Institutions
14-Nov-2001


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