Navigation Links
Agent orange chemical, dioxin, attacks the mitochondria to cause cancer, says Penn research team
Date:12/17/2007

PHILADELPHIA 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 Penns School of Veterinary Medicine and the studys 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.


'/>"/>

Contact: Jordan Reese
jreese@upenn.edu
215-573-6604
University of Pennsylvania
Source:Eurekalert

Related medicine news :

1. Is 4 agents decoction (Si Wu Tang) efficacious in treating primary dysmenorrhea?
2. Investigational Agent Targeting Metabotropic Glutamate 2/3 Receptors Demonstrates Antipsychotic Activity in Humans, Study in Nature Medicine Finds
3. Replidyne Pipeline Featured at 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy
4. MassMutual Agent Honored by Insurance Industry for Extraordinary Service to Client
5. Sagent Pharmaceuticals Inc. Completes $53 Million Series A Financing
6. ABR-Affinity BioReagents Expands 100% Quality Guarantee
7. Inside job: new radioactive agents for colon cancer work inside cells
8. ABR -- Affinity BioReagents Announces Launch of New Website
9. The Bank of New York Mellon Recognized as Change Agent Shaping the Direction of Healthcare Transaction Processing
10. EpiCept to Present Preclinical Studies of EPC2407 in Combination With Anti-Angiogenic and Chemotherpeutic Agents at the AACR-NCI-EORTC International Conference
11. Imagentix Offers Extension of Warrants
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/24/2016)... , ... June 24, 2016 , ... People across the ... Genome magazine’s Code Talker Award, an essay contest in which patients and their families ... to be presented at the 2016 National Society of Genetic Counselors (NSGC) Annual Education ...
(Date:6/24/2016)... , ... June 24, 2016 , ... ... is proud to recognize Dr. Barry M. Weintraub as a prominent plastic surgeon ... beautiful women in the world, and the most handsome men, look naturally attractive. ...
(Date:6/24/2016)... Frederick, Maryland (PRWEB) , ... June 24, 2016 ... ... Mid-Atlantic Angels is actively feeding the Frederick area economy by obtaining investment capital ... support over the past 2½ years that have already resulted in more than ...
(Date:6/24/2016)... ... June 24, 2016 , ... Venture Construction Group (VCG) ... held on June 20th at the Woodmont Country Club at 1201 Rockville Pike, ... organization dedicated to helping service members that have been wounded in battle and their ...
(Date:6/24/2016)... , ... June 24, 2016 , ... ... supporting the upcoming 2016 Miss Arizona pageant as its official Medspa Sponsor. Dr. ... Tempe, Mesa, and Chandler, Arizona. , Dr. Olson says the decision to ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016  American Respiratory Labs (ARL), a ... now able to perform sophisticated lung assessments in patients, homes, thanks ... Inc. Patients are no longer limited to having ... PRO ® , ARL patients like Jeanne R. of ... the comfort of her own home. ...
(Date:6/24/2016)... June 24, 2016 According to ... Type (Standard Pen Needles, Safety Pen Needles), Needle Length ... Growth Hormone), Mode of Purchase (Retail, Non-Retail) - Trends ... report studies the market for the forecast period of ... USD 2.81 Billion by 2021 from USD 1.65 Billion ...
(Date:6/24/2016)... , Belgium , June 24, ... VNRX), today announced the appointment of Dr. ... Directors as a Non-Executive Director, effective June 23, ... Audit, Compensation and Nominations and Governance Committees.  As ... Futcher will provide independent expertise and strategic counsel ...
Breaking Medicine Technology: