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Cigarette smoke causes breaks in DNA
Source: (cancerfacts.com)
Thursday, September 30, 2004
PITTSBURGH – Oct. 1, 2004 – Scientists have long known that cigarette smoke causes lung cancer, but until now, no one has ever shown the mechanism that triggers the cascade of events resulting in cancerous lung cells.
Researchers led by Dr. William Saunders of the University of Pittsburgh are the first to show that cigarette smoke causes chromosome instability. Their research shows how just one or two puffs of a cigarette can cause breaks in DNA leading to defects in a cell's chromosomes. Such genetic instability can result in irreversible changes in genetic information being passed to a newly divided cell.
"Double-stranded breaks are considered the most mutagenic type of DNA damage because the broken ends can fuse to other chromosomes in the cell," Saunders said in a news release. "Chromosome fusion is detrimental to normal chromosome segregation, which in turn leads to genetic imbalances."
The research findings will be reported Tues. Oct. 5 in Pittsburgh at the 35th Annual Meeting of the Environmental Mutagen Society, entitled, "Genes, Mutations and Disease: The Environmental Connection," taking place Oct. 2 to 6. The study will also appear in an upcoming article in the journal Mutation Research.
Before a cell undergoes division, its DNA is duplicated and compressed into identical copies of each chromosome inside the cell nucleus. The chromosomes are then segregated during cell division, so that each daughter nucleus receives a complete copy of the genetic material. The stage when chromosomes are segregated and become separated is called anaphase. Normally, each set of chromosomes is pulled with equal force in opposite directions so that each daughter cell receives the same number of chromosomes.
But when the researchers exposed cells in culture to cigarette smoke, they found that the fused chromosomes were being pulled simultaneously from both directions much like a piece of taffy, forming so-called anaphase bridges between its 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.
Cigarette smoke contains some 5,000 organic compounds, including chemicals known to cause cancers. While the researchers did not expose cells to actual puffs of smoke, the cigarette smoke condensate they used was derived from burning real cigarettes and obtained from the R.J. Reynolds Tobacco Company. Containing mostly particulates, the extracted smoke was liquefied as part of a solvent mixture before the cells were exposed to it.
"Others have found the presence of anaphase bridges is correlated with chromosome instability in cancer cells. 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," said Saunders.
According to their results, 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, agents that block formation of reactive oxygen species, prevented most occurrences of anaphase bridge formation and significantly reduced genomic imbalances.
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