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. The results of their study are published in the June 1 issue of Cancer Research, a journal of the American Association for Cancer Research. "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. 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. The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

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