Male mice breathing city air carry more mutations.
Air pollution can cause DNA mutations in the sperm of mice reared in an industrial city, researchers have found. The results add to ongoing concerns about the effects of air pollution on human health and fertility.
The mice, reared in cages kept in a shed downwind of two steel mills and a busy highway in a Canadian city, showed a host of genetic changes compared to similarly housed mice breathing filtered air. DNA in the sperm of the mice in the polluted area contained 60% more mutations, had more strand breaks, and had more bases that had been chemically modified via the addition of a methyl group. That modification, called DNA methylation, can affect whether a gene is expressed.
All of these changes could, in theory, alter gene expression and function in offspring of these mice, but that has not yet been directly tested.
"It's important to move this forward to the next step: determining whether there are any human corollaries to this," says Jonathan Samet, an epidemiologist at the Bloomberg School of Public Health at Johns Hopkins University in Baltimore, Maryland.
Air pollution has been linked to respiratory and cardiovascular difficulties, developmental defects and lung cancer in humans. But researchers have only begun to tackle the effect of pollution on sperm.
?There has been work on the reproductive effects of pollution, but that has largely focused on outcomes of pregnancy, not on male effects,? says Samet.
Epidemiological studies in humans have suggested a link between air pollution and reduced male fertility, but such studies are often confounded by other lifestyle differences such as diet, genetic background, and economic class. No such research has been done on people in Hamilton Harbour, Canada, where the mouse studies were carried out.
Previous work had demonstrated that the offspring of wild birds that breed near steel mills inherit more DNA mutations than their rural counterparts. Then, studies in mice suggested a possible reason for that pattern. Canadian researchers found that filtering out particles from polluted air lessened the risk of heritable mutations in mice caged near Hamilton1. And the bulk of mutations from pollution were coming from the father2.
Now, in work published this week in the Proceedings of the National Academy of Sciences USA3, Carole Yauk of Health Canada in Ottawa and her colleagues have returned to Hamilton. This time they monitored male mice for direct evidence of DNA damage in their sperm.
After three weeks of breathing the Hamilton air, the mice were already showing more signs of DNA breakage than control mice breathing filtered air. At 10 weeks, their DNA was significantly more methylated than controls. And 16 weeks after the experiment began, their DNA contained more mutations at a specific site than the controls.
Precisely how the pollution caused the DNA damage remains unclear. "It's quite a leap to go from a lungful of air to damaging germ cells in the testes of these mice," says Christopher Somers, a biologist at the University of Regina in Saskatchewan and an author on the study.
The researchers also tested the DNA for signs of direct mutagenesis by a class of chemical compounds called polycyclic aromatic hydrocarbons. Although these compounds are known to cause mutations and are enriched in the Hamilton air, there were no signs that they were responsible for the damage.
That could mean that the changes may be a more general response to particulate pollution, says Somers. For instance, metals bound to the particulates can favour the production of chemically reactive forms of oxygen called reactive oxygen species.
"If that?s the mechanism, you might think that it has general applicability to other sources of pollution, not just steel mills," says Samet.
Somers, C. M., McCarry, B. E., Malek, F. & Quinn, J. S. Science 304, 1008?1010 (2004).
Somers, C.M. et al. Proc. Natl Acad. Sci. USA 99, 15904-15907 (2002)
Yauk, C. et al. Proc. Natl Acad. Sci. USA 105, 605-610 (2008).
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Ledford, H. Air pollution causes sperm mutations. Nature (2008). https://doi.org/10.1038/news.2008.439