Smoking Mice Have Inheritable DNA Changes In Sperm

OTTAWA, Ontario, June 4 -- Men ought to swear off cigarettes long before they even think of having children, according to researchers here.

That's because experiments on mice show that smoking tobacco causes inheritable changes in the DNA of the stem cells that produce sperm, said Carole Yauk, Ph.D., of Health Canada's mutagenesis section.

The finding "suggests that the consequences of smoking extend beyond the smoker to their nonsmoking descendents," Dr. Yauk and colleagues reported in the June 1 issue of Cancer Research.

While it has long been known that smoking causes DNA strand breaks and mutations in somatic cells, such as buccal cells and lymphocytes, this is the first evidence that tobacco causes inheritable mutations, the researchers said.

"Here we are looking at male germline mutations, which are mutations in the DNA of sperm," Dr. Yauk said. "If inherited, these mutations persist as irreversible changes in the genetic composition of offspring."

"We have known that mothers who smoke can harm their fetuses," she said, "and here we show evidence that fathers can potentially damage offspring long before they may even meet their future mate."

The researchers exposed mice to two cigarettes a day, using a system that delivered cigarette smoke at a rate of 0.08 liters per minute, over a period of either six or 12 weeks.

In both cases, the experiment time included an initial two-week lead-in period, during which the mice were given one cigarette a day for the first week and two for the second.

Control mice were placed in similar exposure chambers but not given any smoke.

At the end of the six- or 12-week experiments, the mice were kept without cigarettes for another six weeks to allow for the maturation of the spermatogonial stem cells.

Analysis of the stem cells found that a non-coding region of repeated portions of DNA, called Ms6-hm, was significantly altered in the mice who had been smoking, compared to the controls.

Specifically, the frequency of mutations in the smoking mice, compared with the controls, was:

• 44% greater after six weeks. The ratio was 1. 44, with a 95% confidence interval from 0.87 to 2.39, which was not significant.
• 69% greater after 12 weeks. The ratio was 1.69, with a 95% confidence interval from 1.05 to 2.73, which was significant at P=0.0442.

Overall, the smoking mice had 56% more mutations than the controls, which was significant at P=0.0214.

While the regions tested did not contain any known genes, the mutation rate there correlates with rates in coding regions, the researchers said, implying that smoking is likely to cause inheritable changes to male DNA.

"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," Dr. Yauk said.

"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," she added.