Cigarette Smoke Alters DNA In Sperm, Genetic Damage
Could Pass To Offspring

Science Daily — The science has long been clear that
smoking causes cancer, but new research shows that
children could inherit genetic damage from a father
who smokes. Canadian researchers have demonstrated in
mice that smoking can cause changes in the DNA
sequence of sperm cells, alterations that could
potentially be inherited by offspring.
"Here we are looking at male germline mutations, which
are mutations in the DNA of sperm. If inherited, these
mutations persist as irreversible changes in the
genetic composition of off-spring." said Carole Yauk,
Ph.D., lead author of the study and research scientist
in the Mutagenesis Section of Health Canada's
Environmental and Occupational Toxicology Division.
"We have known that mothers who smoke can harm their
fetuses, and here we show evidence that fathers can
potentially damage offspring long before they may even
meet their future mate."

Males, whether they are mouse or man, generate a
constant supply of new sperm from self-renewing
spermatogonial stem cells. Yauk, along with colleagues
at Health Canada and McMaster University, studied the
spermatogonial stem cells of mature mice that had been
exposed to cigarette smoke for either six or 12 weeks
to look for alterations in a specific stretch of
repeated portions of DNA, called Ms6-hm, which does
not contain any known genes. The "smoking" mice were
exposed to two cigarettes per day, the equivalent --
based on blood levels of tobacco by-products -- of an
average human smoker, according to research previously
published by one of the study's co-authors.

Yauk and her colleagues found that the rate of Ms6-hm
mutations in the smoking mice were 1.4 times higher
than that of non-smoking mice at six weeks, and 1.7
times that of non-smoking mice at 12 weeks. "This
suggests that damage is related to the duration of
exposure, so the longer you smoke the more mutations
accumulate and the more likely a potential effect may
arise in the offspring," Yauk said.

According to Yauk, previous studies have shown that
Ms6-hm and similar locations of non-coding DNA are
sensitive to damage from radiation, mutagenic
chemicals and intense industrial air particulate
pollution. While the researchers did not specifically
study the protein-coding regions of DNA where genes
reside, Yauk notes that previous studies correlate
mutations in non-coding regions with those in coding
regions, and that some repetitive regions of DNA (not
exam-ined in this study) are associated with genes.

"It stands to reason that mutations could also
interfere with genes, but our ongoing research looks
to clarify the severity of DNA damage throughout the
genome," said Yauk. "So, while some men say they'll
quit smoking after their child is born, this
represents a good reason to quit well in advance of
trying to conceive."

Among the next steps in gaining a better understanding
of the germline genetic health conse-quences of
smoking, Yauk and her colleagues plan to study how
altered DNA manifests itself in the children and
grandchildren of male mice that are exposed to
firsthand smoke. They also plan to study the effects
of secondhand smoke on male mice as well the
possibility that the eggs of females are affected by
smoke.

The results of their study are published in the June 1
issue of Cancer Research, a journal of the American
Association for Cancer Research.

Yauk's colleagues include fellow researchers from
Health Canada and Martin Stämpfli, Ph.D., and his
laboratory team at McMaster University. Funding for
this research was provided by grants from the Canadian
Regulatory System for Biotechnology and the Canadian
Institutes of Health Research.

Note: This story has been adapted from a news release
issued by American Association for Cancer Research.


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