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Cigarette smoke blocks cell repair mechanism, University of Florida study shows

air appears to be compromised when chemical components of smoke activate a key gene. That gene interacts with an enzyme that plays a crucial role in repairing damaged DNA, preventing it from doing its job. The cell, despite its mutated form, can then multiply wildly.

A cell with damaged DNA has one of two fates, said Narayan, also a member of the UF Shands Cancer Center.

"Its DNA repair machinery can be enhanced and it can fix the damaged DNA and restore genomic stability, or if the DNA repair machinery becomes compromised within the cell, then it can lead to an accumulation of mutations because the DNA is not fixed before the cell begins to divide," he said. "The mutation then becomes a permanent part of the genome and causes genomic instability, and genomic instability can bring about several cellular dysfunctions, and one of them can lead to tumor formation."

Other UF research led by Xingming Deng, M.D., Ph.D., and published last month in the Journal of Biological Chemistry revealed that nicotine activates a protein in cancer cells that helps them live long, spread to new sites and grow resistant to chemotherapy.

Narayan's team has previously studied cells that were exposed to the chemicals found in cigarette smoke yet did not die. In general, about two-thirds of these cells will be growth-retarded, and some actually acquire cancer-like characteristics, he said.

"Some of these cells that survive are really acquiring true mutagenic characteristics," Narayan said. "A defect in only one cell is important for growth of a full-blown tumor. You don't need 1,000 or 1 million cells to be affected. Only a single cell which may have genomic instability due to compromised DNA repair capacity of the cell can be sufficient for a tumor to develop. That has to be considered also when we do these kinds of studies."

Narayan said the next step will be to find ways to manipulate cells' capacity for DNA repair and to prevent tu
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Source:University of Florida


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