Diesel Exhaust Linked to Cancer Development Via New Blood Vessel Growth

Ohio scientists have demonstrated that diesel exhaust induces the growth of new blood vessels that send blood to supply to solid tumors. This is the first evidence of how exposure to diesel fumes can cause cancer.

The researchers found that more new blood vessels sprouted in mice exposed to diesel exhaust than did in mice exposed to clean, filtered air. The same changes happened in both healthy mice and in sick animals. This suggests, the scientists say, that previous illness isn’t required to make humans susceptible to the damaging effects of the diesel exhaust.

Diesel smoke, photo: EPAMost people only notice diesel fumes when obvious streams of dirty smoke can be seen and smelled from idling buses or from trucks lacking exhaust filters. But the particles of diesel exhaust whose impact these Ohio scientists are concerned about are virtually invisible to the naked eye.

The tiny size of inhaled diesel particles, most less than 0.1 microns in diameter, potentially enables them to penetrate the human circulatory system, organs and tissues, meaning they can do this damage just about anywhere in the body. A micron is one millionth of a meter.

Diesel exhaust exposure levels in the study, the scientists say, were designed to mimic the exposure people might experience while living in urban areas and commuting in heavy traffic. The levels were lower than or similar to those typically experienced by workers who use diesel-powered equipment, who tend to work in mines, on bridges and tunnels, along railroads, at loading docks, on farms and in vehicle maintenance garages, according to the U.S. Department of Labor.

"The message from our study is that exposure to diesel exhaust for just a short time period of two months could give even normal tissue the potential to develop a tumor," said Qinghua Sun, senior author of the study and an assistant professor of environmental health sciences at Ohio State University.

"We need to raise public awareness so people give more thought to how they drive and how they live so they can pursue ways to protect themselves and improve their health. And we still have a lot of work to do to improve diesel engines so they generate fewer particles and exhaust that can be released into the ambient air."

The research appears online and is scheduled for later print publication in the journal Toxicology Letters.

Though some blood vessel growth and chemical changes could be seen in the mice after two weeks of exposure, "generally, the longer the exposure, the more effects we could see," said Sun, also an investigator in Ohio State’s Davis Heart and Lung Research Institute. "It’s difficult to translate outcomes from an animal study directly to the human experience, but the bottom line is, the shorter the exposure to diesel exhaust, the better."

In mice, exposure to diesel exhaust caused a four- to six-fold increase in new blood vessel formation after eight weeks compared to mice breathing filtered air.

The researchers found that three types of blood vessel development occurred in the mice after exposure to the diesel exhaust: angiogenesis, the development of new capillaries; arteriogenesis, the maturation or re-started growth of existing vessels; and vasculogenesis, the formation of new blood vessels.

All of these processes are associated with tumor growth, but unprogrammed angiogenesis in particular can wreak havoc in the human body, Sun said.

"Whenever you talk about a solid tumor, angiogenesis is one of the fundamental mechanisms behind its development. Angiogenesis provides the means for tumor cells to grow because they have to have a blood supply. Without a blood supply, solid tumors will not grow," he said.

"We want our bodies to generate new blood vessels only when we need them. And then stop producing them when we need them to stop."

Though the researchers have not defined every mechanism behind these processes, they sought to explain at least a few ways in which blood vessels are able to sprout or mature after exposure to diesel exhaust.

  • They observed that diesel exhaust exposure activated a chemical signal, vascular endothelial growth factor, which has long been associated with new blood vessel developmen/li>
  • The exposure also increased levels of a protein, hypoxia-inducible factor 1, that is essential to blood vessel development when oxygen levels are low.
  • At the same time, the presence of the exhaust lowered the activity of an enzyme that has a role in producing substances that can suppress tumor growth.

he scientists also tracked low-grade inflammation in tissues exposed to the exhaust, which is often associated with tumor development.

Though the tiny size of diesel exhaust particles may contribute to their ability to penetrate all areas of the body, Sun noted that their complex chemical composition, and the way in which those chemicals are released once particles enter the body, also influence how they react with human cells.

Gasoline exhaust particles are larger than diesel fume particles, but it’s premature to suggest that they are any less dangerous to humans, Sun said.

"The bigger particles are known to be harmful primarily for upper respiratory tract illnesses. Larger particles also can’t travel long distances – they tend to fall to the ground," he said. "Smaller particles hover in the air for a long time and can have long-term impact on humans when inhaled."

Sun and colleagues are now conducting a study testing whether the exhaust particles promote tumor development and metastasis.


Diesel exhaust exposure induces angiogenesis Toxicol Lett. 2009 Aug 14. [Epub ahead of print]

This work is supported by Health Effects Institute awards and grants from the National Institutes of Health.

Co-authors on the study are Xiaohua Xu and Ling Zheng of Ohio State’s Division of Environmental Health Sciences; Nisharahmed Kherada, Aixia Wang and Sanjay Rajagopalan of the Davis Heart and Lung Research Institute; Xinru Hong of the Department of Obstetrics and Gynecology at Fuzhou General Hospital in Fujian Province, China; Chunli Quan, Morton Lippmann and Lung Chi Chen of the Department of Environmental Medicine at the New York University School of Medicine; and Loren Wold of the Center for Cardiovascular and Pulmonary Research at Nationwide Children’s Research Institute.

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How big is a micron?