DOI: 10.1097/01.COT.0000314428.44910.db
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Issn Print: 0276-2234
Publication Date: 2004/11/10
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Excerpt
The study, by researchers from the University of Pittsburgh led by William S. Saunders, PhD, Associate Professor of Biological Sciences and a researcher with the Oral Cancer Center of Discovery, is the first to show that cigarette smoke causes chromosome instability, a news release noted.
While most research has focused on the changes in DNA sequence caused by cigarette smoke, little attention has been given to how smoke affects genomic stability of cells. In laboratory studies using human fibroblasts, exposure to even a small amount of cigarette smoke condensate—equal to about 1/25 of a cigarette—was found to cause breaks to both strands of DNA and compromise the integrity of the cell's chromosomes.
While the researchers did not expose cells to actual puffs of smoke, the cigarette smoke condensate used was derived from burning real cigarettes. Containing mostly particulates, the extracted smoke was liquefied as part of a solvent mixture before it was exposed to the cells.
“Double-stranded breaks are considered the most mutagenic type of DNA damage because the broken ends can fuse to other chromosomes in the cell,” Dr. Saunders explained. “Chromosome fusion is detrimental to normal chromosome segregation, which in turn leads to genetic imbalances.”
When the researchers exposed cells in culture to cigarette smoke, they found that the fused chromosomes were being pulled simultaneously from both directions, forming so-called anaphase bridges between the two ends.
Eventually, these chromosomes either tear apart, leaving two broken pieces, or if they don't break apart, the abnormal, elongated chromosomes may persist after anaphase is completed. Either way, a major change in the structure of the chromosomes is the end result.
“Others have found the presence of anaphase bridges is correlated with chromosome instability in cancer cells,” Dr. Saunders said. “Because cigarette smoking is linked to oral, larynx, lung, bladder, and esophageal cancers, our results showing that cigarette smoke can produce anaphase bridges and destabilize a cell's chromosomes have added significance.”
Li Z. Luo, PhD, a graduate student who presented the data, noted in the news release that the failure of the cell to accurately repair the cigarette smoke condensate-induced double-stranded breaks probably leads to anaphase bridge formation and chromosomal instability.
As noted in the published study in an upcoming issue of the journal Mutation Research, the development of anaphase bridges and chromosome instability is most likely due to reactive oxygen species that form as the cell is exposed to the various chemicals in smoke.
Treating the smoke-exposed cells with different antioxidants prevented most occurrences of anaphase bridge formation and significantly reduced genomic imbalances, Dr. Saunders said.
“Unfortunately, no amount of scientific evidence arguing against smoking will get everyone to stop or not begin to smoke in the first place. So, perhaps one long-term goal should be to develop cigarettes that somehow prevent what we've seen happen to the cells in our lab.
