Cigarette smoke causes breaks in DNA

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http://www.cancerfacts.com/Home_News.asp?CancerTypeId=4 & NewsId=1737

 

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.