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