 |
|
Agent orange chemical, dioxin, attacks the mitochondria to cause cancer, says Penn research team
December 18, 2007PHILADELPHIA- Researchers with the University of Pennsylvania School of Veterinary Medicine have demonstrated the process by which the cancer-causing chemical dioxin attacks the cellular machinery, disrupts normal cellular function and ultimately promotes tumor progression.
The team identified for the first time that mitochondria, the cellular sub-units that convert oxygen and nutrients into cellular fuel, are the target of tetrachlorodibenzodioxin, or TCDD. The study showed that TCDD induces mitochondria-to-nucleus stress signaling, which in turn induces the expression of cell nucleus genes associated with tumor promotion and metastasis.
The mechanism the research team has described is directly relevant to understanding incidences of breast and other cancers in human populations exposed to these chemicals. With a better understanding of this underlying cellular mechanism, researchers hope to improve their understanding of tumor growth and promotion.
"Now that we have identified this signaling mechanism we can look at ways to disrupt this complex chain of events," said Narayah Avadhani, chair of the Department of Animal Biology at Penn's School of Veterinary Medicine and the study's lead investigator. "Our ultimate goal is to block the propagation of this mitochondrial stress signaling and inhibit the expression of the proteins that combine to assist cancer growth."
A well-characterized mechanism of TCDD action occurs through activation of arylhydrocarbon receptors, AhR, by directly binding to the protein subunits. Activated AhR mediates the transcriptional activation of many genes including those involved in fatty acid metabolism, cell cycle regulation and immune response. The present study, however, shows that TCDD starts the chain of events that promote tumor progression in vivo by directly targeting mitochondrial transcription and induction of mitochondrial stress signaling. A unique feature of this TCDD-induced signaling is that it does not involve the action of AhR but occurs through increased calcium levels in cells and activation of calcium responsive factors. A net result of signaling cascade is slowing down of cellular apoptosis, increased cell proliferation and tumor cell metastasis. Taken together, this study describes a novel mechanism of TCDD-induced tumor progression and emergence of metastatic cancer cells.
TCDD is the most toxic compound in the dioxin family. Formed as a by-product during waste incineration, paper, chemical and pesticide manufacturing, it was the toxic ingredient in Agent Orange and closed the Love Canal in Niagara Falls. The public health impact of dioxin, according to the Environmental Protection Agency, compares to that of the pesticide DDT.
University of Pennsylvania
"Now that we have identified this signaling mechanism we can look at ways to disrupt this complex chain of events," said Narayah Avadhani, chair of the Department of Animal Biology at Penn's School of Veterinary Medicine and the study's lead investigator. "Our ultimate goal is to block the propagation of this mitochondrial stress signaling and inhibit the expression of the proteins that combine to assist cancer growth."
A well-characterized mechanism of TCDD action occurs through activation of arylhydrocarbon receptors, AhR, by directly binding to the protein subunits. Activated AhR mediates the transcriptional activation of many genes including those involved in fatty acid metabolism, cell cycle regulation and immune response. The present study, however, shows that TCDD starts the chain of events that promote tumor progression in vivo by directly targeting mitochondrial transcription and induction of mitochondrial stress signaling. A unique feature of this TCDD-induced signaling is that it does not involve the action of AhR but occurs through increased calcium levels in cells and activation of calcium responsive factors. A net result of signaling cascade is slowing down of cellular apoptosis, increased cell proliferation and tumor cell metastasis. Taken together, this study describes a novel mechanism of TCDD-induced tumor progression and emergence of metastatic cancer cells.
TCDD is the most toxic compound in the dioxin family. Formed as a by-product during waste incineration, paper, chemical and pesticide manufacturing, it was the toxic ingredient in Agent Orange and closed the Love Canal in Niagara Falls. The public health impact of dioxin, according to the Environmental Protection Agency, compares to that of the pesticide DDT.
University of Pennsylvania
Dioxin Current Events and Dioxin News RSSExposure to Agent Orange linked to prostate cancer in Vietnam veterans
UC Davis Cancer Center physicians today released results of research showing that Vietnam War veterans exposed to Agent Orange have greatly increased risks of prostate cancer and even greater risks of getting the most aggressive form of the disease as compared to those who were not exposed.
Researchers identify cancer preventive properties in common vitamin supplement
Early laboratory research has shown that resveratrol, a common dietary supplement, suppresses the abnormal cell formation that leads to most types of breast cancer, suggesting a potential role for the agent in breast cancer prevention.
New study links fate of personal care products to environmental pollution and human health concerns
Parental concerns in maintaining germ-free homes for their children have led to an ever-increasing demand and the rapid adoption of anti-bacterial soaps and cleaning agents. But the active ingredients of those antiseptic soaps now have come under scrutiny by the EPA and FDA, due to both environmental and human health concerns.
Firing clay in unvented kilns may be a source of exposure to dioxins
Firing clay in unvented kilns could be a significant source of dioxins in people exposed regularly and over long periods, a new study suggests.
Veterans exposed to Agent Orange have higher rates of prostate cancer recurrence
Veterans exposed to Agent Orange have a 48 percent increased risk of prostate cancer recurrence following surgery than their unexposed peers, and when the disease comes back, it seems more aggressive, researchers say.
Exposure to dioxins influences male reproductive system, study of Vietnam veterans concludes
A dioxin toxin contained in the herbicide Agent Orange affects male reproductive health by limiting the growth of the prostate gland and lowering testosterone levels.
Test for Dioxin Sensitivity in Wildlife Could Result from New Study
Why are chickens so sensitive to dioxins, but terns seem much more resistant, despite their exposure through eating dioxin-tainted fish? The life-or-death difference researchers have found can be partially explained by two amino acids in the chain of 858 amino acids that form one critical protein.
One gene provides fruit fly both antenna and color vision
A team of researchers that includes biologists from Washington University in St. Louis has discovered that a gene involved in the development and function of the fruit fly antenna also gives the organism its color vision.
Environmental chemicals implicated in cancer, say experts
New research at the University of Liverpool suggests that environmental contaminants, such as pesticides, are more influential in causing cancer than previously thought.
EU research suggests that PCBs damage sperm - but finds no dramatic effect on male fertility
Research by an EU-supported international team of scientists has shown that polychlorinated biphenyls (PCBs)[1]-synthetic organic chemicals found widely in the environment and absorbed in the diet - may damage sperm.
More Dioxin Current Events and Dioxin News Articles
 | Dioxin, Agent Orange: The Facts by Michael Gough |
 | Biodegradation of Dioxins and Furans (Environmental Intelligence Unit) Bioremediation of organic pollutants and heavy metals by use of microorganisms represents a safe, inexpensive, and environmentally-friendly concept in modern environmental engineering. During the last three decades intense efforts have been made by microbiologists and environmental engineers in the isolation and characterization of microorganisms capable of degradation, transformation and... |
 | Dioxin Perspectives:: A Pilot Study on International Information Exchange on Dioxins and Related Compounds (Nato - Challenges of Modern Society) |
 | Dying from Dioxin: A Citizen's Guide to Reclaiming our Health and Rebuilding Democracy by Lois Marie Gibbs It's in our food. It's in our bodies. And it's making us sick. According to recently released studies from the EPA, widespread exposure to dioxin is destroying the health of the American people. In Dying from Dioxin, Lois Marie Gibbs and grassroots activists and scientists with the Center For Health, Environment and Justice (formerly the Citizens Clearinghouse for Hazardous Waste) describe... |
 | The Dioxin War: Truth and Lies About a Perfect Poison by Robert Allen This is a book about Dioxin, one of the most poisonous chemicals known to humanity. It was the toxic component of Agent Orange, used by the US military to defoliate huge tracts of Vietnam during the war in the 60s and 70s. It can be found in pesticides, plastics, solvents, detergents and cosmetics. Dioxin has been revealed as a human carcinogen, and has been associated with heart disease, liver... |
 | Dioxins and Health Dioxins are the most potent, well known, and long lasting of the persistent organic pollutants (POPS), and are of great interest in public health, toxicology, chemistry, medicine, law, and to regulatory agencies worldwide. In the years since publication of the first edition of Dioxins and Health, major advances have been made in human epidemiology as well as in animal studies. The second edition... |
 | Dioxins: An overview [An article from: Environmental Research] by A. Schecter, L. Birnbaum, J.J. Ryan, J. Constable This digital document is a journal article from Environmental Research, published by Elsevier in 2006. The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser.Description: This review article summarizes what is known about human health following exposure to dioxins. It is meant primarily for health... |
| Dioxin in the Environment: Its Effect on Human Health by Fellman | |
 | Decades of Dioxin by Warren B. Crummett |
 | Effects of oxygen, catalyst and PVC on the formation of PCDDs, PCDFs and dioxin-like PCBs in pyrolysis products of automobile residues [An article from: Chemosphere] by H.T. Joung, Y.C. Seo, K.H. Kim This digital document is a journal article from Chemosphere, published by Elsevier in 2006. The article is delivered in HTML format and is available in your Amazon.com Media Library immediately after purchase. You can view it with any web browser.Description: End-of-life vehicles are dismantled to recover reusable parts and then sent to a shredding facility for steel material recovery. The... |
| © 2008 BrightSurf.com |