In the Lab

• By Hannah R. Kolni
• Nov 01, 2006

Researhcers: Airborne Metal Particles From Pollution Could Lead To Lung Cancer
The ecological study, published on Sept. 15 in the Journal of Thoracic Oncology, is the first study of its kind in a large population that compared incidence rates of lung cancer for all 254 Texas counties from 1995 to 2000 with industrial air releases of metals reported to EPA in the previous eight- to 13-year period (1988-2000).

The researchers from the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern found that the lung cancer rates were highest in counties with the highest level of industrialization. These counties were primarily located in the Houston area and the contiguous Gulf Coast counties and in the Dallas-Fort Worth metropolitan area, where there also were higher industrial emissions of zinc, chromium and copper.

The study's findings point to potential root causes for lung cancer in the estimated 10 percent to 15 percent of lung cancer patients who never smoked, said Dr. Yvonne Coyle, associate professor of internal medicine and the study's senior author.
"There is concern that other environmental carcinogens may be interacting with cigarette smoking or alone may be influencing the current trends for lung cancer incidence and mortality," Coyle said.

Explaining the cancer-causing effect of airborne metals, Coyle said: "There is some evidence that metals can interfere with a biochemical process called methylation that inactivates genes that normally suppress tumor growth.

"Although the study is not conclusive, it provides new information suggesting that airborne metals, including those that are essential human nutrients, such as zinc and copper, play an important role in lung carcinogenesis."

The researchers acknowledged that although this study provides evidence that metals in air pollution are associated with lung-cancer risk in a large population or a group of individuals, it will be important for future studies to determine whether individuals with lung cancer have actually had previous high exposures to airborne metals.

The research was supported by the National Cancer Institute's Specialized Program of Research Excellence in Lung Cancer at UT Southwestern and the Clay Weed Memorial Trust Fund.

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Biodegradable Napkin Could Quickly Detect Biohazards
Detecting bacteria, viruses, and other dangerous substances in hospitals, airplanes, and other settings could soon be as simple as wiping a napkin or paper towel across a surface, according to a researcher from Cornell University.

"It's very inexpensive; it wouldn't require that someone be highly trained to use it; and it could be activated for whatever you want to find," said Margaret Frey, the Lois and Mel Tukman assistant professor of Fiber Science and Apparel Design at Cornell. "So if you're working in a meat-packing plant, for instance, you could swipe it across some hamburger and quickly and easily detect E. coli bacteria."

Once fully developed, the biodegradable absorbent wipe would contain nanofibers containing antibodies to numerous biohazards and chemicals and would signal by changing color or through another effect when the antibodies attached to their targets. Users would simply wipe the napkin across a surface; if a biohazard were detected, the surface could be disinfected and retested with another napkin to be sure it was no longer contaminated.

In work conducted with Yong Joo, assistant professor of chemical and biomolecular engineering, and Antje Baeumner, associate professor of biological and environmental engineering, both at Cornell, Frey developed nanofibers with platforms made of biotin, a part of the B vitamin complex, and the protein streptavidin, which can hold the antibodies. Composed of a polymer compound made from corn, the nanofibers could be incorporated into conventional paper products to keep costs low. Nanofibers, with diameters near 100 nanometers (a nanometer is one-billionth of a meter, or about three times the diameter of an atom), provide extremely large surface areas for sensing and increased absorbency compared with conventional fibers.

"The fabric basically acts as a sponge that you can use to dip in a liquid or wipe across a surface," Frey said. "As you do that, antibodies in the fabric are going to selectively latch onto whatever pathogen they match. Using this method we should, in theory, be able to quickly activate the fabric to detect whatever is the hazard of the week, whether it is bird flu, mad cow disease or anthrax."

Frey and her colleagues are still working on ways, such as color change, for the fabric to signal that it has identified the contaminant.

"We're probably still a few years away from having this ready for the real world," Frey said, "but I really believe there is a place for this type of product that can be used by people with limited training to provide a fast indication of whether a biohazard is present."

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Study Finds Environmental Toxin Causes Heritable Adult-onset Diseases
A disease you are suffering today could be a result of your great-grandmother being exposed to an environmental toxin during pregnancy -- and you may already have passed it along to your children.

Researchers at Washington State University (WSU) found that exposure to an environmental toxin during embryonic development can cause an animal, and almost all of its descendents, to develop adult-onset illnesses such as cancer and kidney disease. Their discovery suggests that toxins may have played a role in the rapid increase in localized geographic areas of diseases that were previously thought to be caused primarily by genetic mutations.

"It's a new way to think about disease," said Michael K. Skinner, director of the Center for Reproductive Biology. "If this pans out, it gives us a host of new diagnostic and therapeutic tools." He said it also underscores the potential long-term hazards of environmental contaminants.

The work is reported in two papers in the September 14 issue of the journal Endocrinology. It builds on the group's 2005 finding that exposure to a toxin during embryonic development can cause fertility problems in male rats that are passed to later generations.

In the current study, Skinner and a team of WSU researchers exposed pregnant rats to an environmental toxin during the period that the sex of their offspring was being determined. At that stage of development, the genes of the male embryo's sex cells (future sperm) are uniquely vulnerable to reprogramming.

The researchers used vinclozolin, a fungicide commonly used in vineyards. Vinclozolin belongs to the class of compounds called endocrine disruptors, synthetic chemicals that interfere with the normal functioning of reproductive hormones. Skinner's group used higher levels of the toxin than are normally present in the environment, but their study raises concerns about the long-term impacts of such toxins on human and animal health, particularly in exposures during early- to mid-pregnancy (six weeks to five months in humans). Further work will be needed to determine whether lower levels have similar effects.
Pregnant rats that were exposed to vinclozolin produced male offspring with low sperm counts and a high incidence of adult-onset diseases. Despite their low fertility, those males were still able to produce offspring. When they were mated with females that had not been exposed to the toxins, their offspring had the same problems. The effect persisted through four generations, with about 85 percent of the offspring in each generation developing conditions such as breast tumors, prostate disease, kidney disease, immune system abnormalities, and premature aging. Some mice came down with just one disease, but the majority suffered multiple ailments.

"Only the original generation mother was exposed to the environmental toxicant," Skinner said. "A human analogy would be if your grandmother was exposed to an environmental toxicant during mid-gestation, you may develop a disease state even though you never had direct exposure, and you may pass it on to your great-grandchildren."

The study shows the potential impact of so-called epigenetic inheritance, which refers to the transmission from parent to offspring of biological information that is not encoded in the DNA sequence. Instead, the information stems from small chemicals, such as methyl groups, that become attached to the DNA. In epigenetic transmission, the DNA sequences remain the same, but the chemical modifications change the way the genes work and when they "turn on" and "turn off."

The team identified 25 segments of DNA in the affected rats that had altered patterns of methyl groups compared to control rats. Their results suggest the genes controlling susceptibility to the observed diseases lie somewhere within those 25 segments. Skinner said the broad-spectrum effect of the changes, causing diseases in many organ systems, was a notable result that could provide valuable clues about how diseases develop.

According to Skinner, such changes might play a role in human diseases such as breast cancer and prostate disease, whose frequency is increasing faster than would be expected if they were the result of genetic mutations alone. Scientists have long known about epigenetic changes, but their high rate of heritability and their importance in the control of gene activity were not appreciated until recently.

Skinner said the finding that an environmental toxin can permanently reprogram a heritable trait also may alter our concept of evolutionary biology. Traditional evolutionary theory maintains that the environment is primarily a backdrop on which selection takes place, and that differences between individuals arise from random mutations in the DNA. The work by Skinner and his group raises the possibility that environmental factors may play a much larger role in evolution than has been realized before.

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This editorial originally appeared in the November/December 2006 issue of Environmental Protection, Vol. 17, No. 9.

This article originally appeared in the 11/01/2006 issue of Environmental Protection.