UW scientists find increased risk of breast cancer from exposure to a component of diesel exhaust

Center for Ecogenetics & Environmental Health (CEEH) researchers Joel Kaufman and Kerryn Reding are interested in understanding the effects of exposure to air pollution from diesel exhaust on human health. 

Dr. Kaufman, who is also Director of the UW DISCOVER Center: Cardiovascular Disease and Traffic-Related Air Pollution, researches the effects of exposure to fine particulate matter (PM2.5), a component of diesel exhaust, on the cardiovascular system. Recently, Joel discussed his team's work in a podcast for the National Institute of Environmental Health Sciences Partnerships for Environmental Public Health (NIEHS PEPH).

Now, a study by Dr. Kerryn Reding from the UW School of Nursing and Fred Hutchinson Cancer Research Center shows that women exposed to nitrogen dioxide (NO2) have an increased risk of developing the most common form of breast cancer, hormone receptor-positive breast cancer. NO2 is another a component of diesel exhaust.

Some past studies looking for possible connections between breast cancer and air pollution have reported associations with both PM2.5 and NO2. To get a clearer picture, Dr. Reding and her group, who represent the UW Schools of Nursing and Public Health, the Fred Hutchinson Cancer Research Center, University of Bergen, Norway, and the National Institute of Environmental Health Sciences (NIEHS), undertook a large-scale study that spanned 4.5 years. They analyzed data from 47,591 women in the Sister Study, a National Institutes of Health Study of the Environmental and Genetic Risk Factors for Breast Cancer. The researchers adjusted for demographics (age, income, education) and health behaviors (body mass index, smoking) to estimate the risk of developing breast cancer after exposure to NO2, PM2.5 and PM10 from air pollution.

The study found no increased risk of breast cancer from PM2.5 or PM10. In the women who had higher than average exposures to NO2, it found a 10% increased risk of hormone receptor-positive (ER+/PR+) breast cancer. 

People who live or work near major roadways have a higher than average exposures to diesel exhaust and NO2. According to the US Environmental Protection Agency (EPA)48 million people in the United States live within 300 feet of a major highway, railroad or airport. Living near a major roadway confers a higher risk of asthma, cardiovascular disease, impaired lung development and childhood leukemia, low-birthweight babies, and premature death. 

Dr. Reding's research was published in the December 2015 issue of Cancer Epidemiology, Biomarkers & Prevention. Another summary of Dr. Reding’s study was published in UW Health Sciences NewsBeat.

-- Marilyn Hair




Cadmium exposure affects Coho salmon ability to smell ... and why it matters

Chase Williams, PhD candidate in the UW School of Public Health Department of Environmental and Occupational Health Sciences (DEOHS) has defended his dissertation. The title is: Mechanisms and Biomarkers of Cadmium Induced Neurobehavioral Impairment in the Olfactory System of Coho Salmon (Oncorhynchus kisutch).  Dr. Evan Gallagher, Director of the University of Washington Superfund Research Program (UW-SRP) and a member of the Center for Ecogenetics and Environmental Health, was his Supervisory Committee Chair.

Chase Williams
Chase Williams
First, I can't resist observing that the defense was held in Roosevelt 2228, a conference room with glass doors commonly called the Fishbowl.

Pacific salmon populations are threatened by many factors, and one contributing factor is thought to be disruption of the olfactory system, the sense of smell, by waterborne pollutants. The salmon olfactory system is in direct contact with the water column making it a sensitive target for chemical disruption by waterborne pollutants. This is important as salmon rely on their sense of smell for many critical functions, such as navigation, finding food and avoiding predators.


The metal cadmium (Cd) is a common pollutant in industrialized and agricultural waterways. Sources of Cd include discharge from industrial operations and fertilizers used in agricultural areas. Research has shown that Cd can impair the function of the olfactory system in zebrafish and trout. It is also known that wild juvenile salmon migrate through pollutant impacted waterways, many of which can contain Cd. 


Chase investigated three questions: (1) Do acute Cd exposures change salmon behaviors that depend on the sense of smell? (2) Does the olfactory system recover after being exposed to Cd? (3) Can we develop a set of molecular biomarkers that reflect Cd induced olfactory dysfunction and injury?


First, juvenile Coho were exposed to two concentrations of Cd for between 8 and 48 hours, followed by a 16-day recovery period. Chase observed the Cohos’ behavioral responses to an alarm odorant in a two-choice maze, after which he examined their olfactory rosettes for changes in histology (tissue anatomy) and gene expression. 

Here is what he found: Exposure to a low-level (3.7 parts per billion or ppb) and a high-level (347 ppb) of Cd disrupted the Cohos’ "olfactory driven alarm behavior". In addition, the 347 ppb exposure level completely blocked their sense of smell within 48hrs. After the 16-day recovery, the fish exposed to both levels of Cd showed only partial recovery of olfactory function. Tissue analysis of the olfactory sensory epithelium (thin tissue lining of hollow structures) showed that the high-level Cd exposure killed many olfactory sensory and non-sensory epithelial cells, explaining the loss of smell. Gene expression of cellular stress/injury biomarkers that were measured in the olfactory rosettes (hmox1, mt1a, nrn1) hinted at the mechanisms.


Based on those findings, Chase then investigated how exposure to Cd impacted Coho salmon behavioral responses to multiple types of odorants, and the effect of Cd on different types of olfactory sensory neurons. Two experiments were done: (1) Juvenile Coho salmon were exposed to one of two concentrations of Cd (2 and 30 ppb) for 48hrs, followed by 16 days of recovery; (2) Another group of juvenile Coho salmon were exposed to lower-levels of Cd (0.3 and 2 ppb) for 16 days, followed by 16 days of recovery. Chase analyzed olfactory driven behaviors in a two-choice maze, using odorants that elicited 3 possible responses: an attraction, an avoidance, or an alarm response. Following the behavioral trials, he again analyzed changes in histology and gene expression within the olfactory rosettes.


What he found was that exposure to Cd altered the Cohos' behavioral responses to the different scents, and in some cases completely reversed their responses, even at the very-low 0.3 ppb Cd exposure level. Surprisingly, these behavioral alterations persisted even after the 16-day recovery period. He found that the low-level Cd exposures did not induce observable injuries in the olfactory sensory epithelial tissue. He also found that Cd builds up quickly and persists in the olfactory sensory epithelium. The accumulation and persistence of Cd in the olfactory system closely mirrored the observed behavioral changes. Analyzing the expression levels of protein and gene markers of the two main types of olfactory sensory neurons, ciliated and microvillar, he found that exposure to the 30 ppb level of Cd predominantly impacted the ciliated olfactory sensory neurons compared to the microvillar olfactory sensory neurons.

A young Coho salmon (photo credit: kellymrk 
http://ian.umces.edu/discforum/index.php?topic=448.0)

Conclusions:

• Exposure to environmentally relevant concentrations of Cd can disrupt salmon olfactory function. There is a partial, but incomplete, recovery of the ability to smell when the exposure ends.

• When the Coho sense of smell is impaired, Coho response to typical odorants changes. Different olfactory neuronal cell types do not all respond the same way to Cd exposures. 

• This data suggest that the mechanisms underlying the behavioral alterations vary depending on the level of Cd exposure. The observed behavioral dysfunction following high-level Cd exposures are likely driven by significant injury to the olfactory epithelium. However, the lack of observable injury to the olfactory epithelium following the low-level Cd exposures suggests that the observed behavioral dysfunction following low-level Cd exposures are most likely driven by disruption of olfactory neuronal signaling.

• The results of this study indicate that juvenile salmon migrating through waterways that contain Cd (and potentially other metals) may have rapid and persistent loss of the ability to smell. An impaired ability for fish to smell has been linked to loss of fitness and increased mortality.

The Superfund Research Program helped to finance this research. Chase was a Student Poster Winner at the 2012 SRP Annual meeting. In 2013 he made a presentation to the SRP Trainee Webinar Series titled: Effects of Cadmium on Olfactory Mediated Behaviors and Molecular Biomarkers in Coho Salmon (Oncorhynchus kisutch). Chase also presented a poster at the 2015 Society of Environmental Toxicology and Chemistry (SETAC) 35th annual meetingDeveloping sensitive markets of cadmium-inhibition of odorant perception in Coho salmon


His work builds on Evan's Gallagher's research on Biochemical Mechanisms of Olfactory Injury in Salmon that can affect salmon survival behaviors such as homing, feeding, and predatory-prey avoidance.   

--Marilyn Hair and Chase Williams



NIEHS Hosts Tribal Ecological Knowledge Workshop

Northwest tribal member harvesting camas
Photo: Jolene Grover
Kelly Edwards and Rose James, co-directors of the Community Outreach and Ethics Core at the Center for Ecogenetics and Environmental Health (CEEH), attended the Tribal Ecological Knowledge Workshop held December 3-4, 2015 in Bethesda, MD. The workshop was hosted by the National Institute of Environmental Health Sciences (NIEHS).

What is Tribal Ecological Knowledge?

Tribal Ecological Knowledge (TEK) is a holistic understanding by indigenous people of their relationship to the earth and the universe. TEK encompasses the spiritual, physical, emotional and mental aspects of a person. It is a way of living in harmony with the land, water and environment as our Creator intended. TEK is a subset of Indigenous Knowledge.

At the workshop, Native presenters explained that Tribal Ecological Knowledge is how they understand the environment we live in. TEK is based on an accumulation of observations, and passed down by the elders. A member of the Yupik community on the coast of Alaska said, "We cannot separate ourselves from our environment. Our way of life is intertwined with our environment."

The TEK workshop explored the contributions Indigenous communities bring to environmental health sciences and biomedical research. NIEHS hopes the workshop will raise awareness of TEK and that input from TEK experts will help identify the best ways to incorporate ancient knowledge and practices into Western research methods. NIEHS wants to increase trust and mutual respect in tribal-academic partnerships.

AI/AN community members and researchers shared spellbinding stories:

On St. Lawrence Island in Alaska, the levels of polychlorinated biphenyls (PCB)* in the marine mammals that are the traditional Yupik foods are hundreds of times higher than the limit recommended by the US Environmental Protection Agency (EPA). Persistent chemicals like PCBs don't stay where they are manufactured or used, and concentrations have been found to increase from south to north, resulting in high concentrations in the Arctic. The Yupik speaker said, "We are being contaminated without our consent." She listed her family members who have cancer or have died of the disease: "It isn't a matter of if I'll get cancer, it's when."

Annie Belcourt (Blackfeet and Hidatsa) from the University of Montana told the traditional story of how the Nez Perce got fire: A boy used his bow and arrow to capture fire from the black buckskin bag in the sky and gave up his life to bring fire to earth. Fire and smoke are sacred, yet too much smoke causes sickness. Ways to improve the use of wood stoves in homes are being explored that preserve the Nez Perce culture and also protect health.

Jose Barreiro (Taino), who works for the Smithsonian National Museum of the American Indian, said that academic papers in the l960s and '70s that came out of research in Cuba propagated the myth that the Taino were going extinct. In the Soviet era, family farms and traditional foods were replaced by large collective farms that grew one crop - sugar - for export to the USSR. The fall of the Soviet Union in 1989-90 resulted in the collapse of the Cuban economy. The Taino remembered the traditional foods and were called upon to bring this knowledge back to help the people survive. Barreiro suggested Cuba as a harbinger for how TEK can help the world address damage to the environment. He admonished the audience to "take TEK seriously, someday you might need it."

The Center for Ecogenetics and Environmental Health poster highlights our own Native TEACH ProjectAmerican Indian Environmental Health Stories.



 NIEHS Director Linda Birnbaum summarized the ideas that stood out for her at the TEK workshop:

We need to recognize what the elders are telling us.
We must bridge, not integrate, TEK and Western science.
The earth is our mother. Mother Earth is in trouble.

-- Marilyn Hair, Rose James, Kelly Edwards

*PCBs are man-made organic chemicals that were used in industrial and commercial applications until they were banned in 1979. PCBs can cause cancer, as well as adverse health effects in the immune, reproductive, nervous, and endocrine systems. PCBs do not readily break down but remain for long periods of time cycling between air, water, and soil. They are taken up into small organisms and fish; people can be exposed by eating fish that contain PCBs. PCBs are found all over the world.  -- EPA