Pollutants in the womb can trigger adult cancers

Mouse study shows fetal exposures may pose long-term risks

Mouse moms exposed late in pregnancy to heavy doses of a carcinogen gave birth to pups that inevitably developed lymphomas and lung cancers, a new study shows. The malignancies generally didn’t show up until the offspring reached the human equivalent of adulthood. The good news: Milk from carcinogen-treated mouse moms posed little added risk.

This demonstration “that very short early-life exposures can have major consequences is very important,” observes toxicologist Linda S. Birnbaum of the Environmental Protection Agency in Research Triangle Park, N.C.

In 2006, David E. Williams and his colleagues at Oregon State University in Corvallis developed an animal model of cancer formation triggered by fetal exposure to pollutants. The team laced the diets of mice with the carcinogen dibenzo[a,l]pyrene — also known as DBP — during just the final two or three days of their three-week pregnancies. This chemical is one of the most toxic of many thousands of polycyclic aromatic hydrocarbons, or PAHs, that form during the incomplete burning of fuels, cigarettes and other carbon-rich materials.  

In their new study, appearing in the Dec. 15 Toxicology and Applied Pharmacology, the Oregon State scientists determined the cancer risk among 215 pups from exposures in the womb compared to any delivered through milk. To do this, the researchers sent half of the pups to foster moms for three weeks. Among these foster pups, those whose moms had been treated with DBP were nursed by untreated mice and the newborns from untreated moms were suckled by mice exposed to pollutants while pregnant.

Although newborns exposed to DBP in the womb appeared healthy and full size, these pups began developing lymphomas within six weeks. By 12 weeks old — the mouse equivalent of people in their 20s — these mice were dying of cancer in rapidly increasing numbers.

Sixty-five percent of mice that had encountered DBP in both the womb and their mother’s milk never reached 10 months old. Among those exposed to the pollutant only during pregnancy, 30 percent succumbed in the first 10 months. Clean newborns sent to suckle from DBP-treated foster moms, by contrast, rarely developed cancer, much less died.

The Oregon State team also linked cancer and survival rates to various forms of a gene responsible for triggering the breakdown of PAHs. Birnbaum, an expert on the toxicity impacts of that Ah-receptor gene, notes that the new genetic data may explain why some animals in each exposure group fared more poorly than the rest.

Williams agrees. The fetal young of exposed moms that had the gene variation for rapid breakdown of PAHs probably received less DBP exposure. And young mice carrying genes for poor breakdown could have experienced an exaggerated exposure.

Overall, Williams says, the new findings “are not what we had been expecting” — that a perhaps two-day exposure at the end of pregnancy would trump, much less vastly overwhelm, doses delivered for three weeks via milk.

To Birnbaum, however, the findings make perfect sense. PAHs are rapidly broken down by detoxification enzymes, she explains. “So the dose transferred lactationally several days after a [mom] was treated could be almost zip.”

Williams says his group will now begin testing what happens if the moms’ exposures continue through lactation. His team will also switch from DBP to a mix of PAHs. This combo was extracted from Beijing’s air last winter and then again during the Olympics, when heavy industry and auto traffic were curtailed.

For most people, save smokers, where pollutant inhalation dominates, “well over half — 60 to 70 percent — of the exposure [to PAHs] is dietary,” Williams says.

One day, diet might prove the route to preventing PAH-linked cancers as well.

Williams’ team has identified a constituent of broccoli and its kin that prevents these malignancies. So, he says, “We might get to a point where we could recommend [foods or supplements] for women that would protect a fetus from carcinogens.”

Janet Raloff is the Editor, Digital of Science News Explores, a daily online magazine for middle school students. She started at Science News in 1977 as the environment and policy writer, specializing in toxicology. To her never-ending surprise, her daughter became a toxicologist.

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