| |
 |
|
|
Science Forum Index » Immunology Forum » Agent Orange ~ Cancer ~ TCDD ~ The Mitochondrial Connection
Page 1 of 1
|
| Author |
Message |
| Ilena Rose |
 Posted: Sun Mar 23, 2008 12:32 pm |
|
|
|
Guest
|
Note from Health Lover, Ilena Rosenthal:
http://ilenarose.blogspot.com
I first begin learning about the ways of Dow Chemical helping a friend
widowed because her 39 year old husband died of various cancers caused
by Agent Orange, attempt to receive some compensation for her young
children and herself.
The amount of time and energy and human resources they put into
covering up the dangers of their deadly products for as long as
possible seems to be without limits.
Cancer and TCDD: The Mitochondrial Connection
By M. Nathaniel Mead
Mar 6, 2008 - 1:44:08 PM
http://foodconsumer.org/7777/8888/M_edicare_54/030601442008_Cancer_and_TCDD_The_Mitochondrial_Connection.shtml
During the Vietnam War, from 1961 to 1971, U.S. military forces
sprayed millions of gallons of the herbicide Agent Orange over vast
tracts of Southeast Asian jungle, mainly in an effort to remove
foliage and expose enemy troops. Troops were exposed to TCDD that
contaminated the Agent Orange, and since the 1970s, elevated blood
TCDD concentrations have been implicated in many cancers, skin rashes,
and other health problems experienced by Vietnam veterans. Although
TCDD is carcinogenic, it is not directly genotoxic. A report in the 8
January 2008 Proceedings of the National Academy of Sciences now
demonstrates one of the ways that TCDD may promote cancer's growth and
spread.
The new study describes a novel mechanism of TCDD action that focuses
on the mitochondria: "We found that TCDD induces tumor cell
proliferation and invasion by directly acting on mitochondrial
transcription machinery and inducing mitochondrial respiratory
stress," says principal investigator Narayan G. Avadhani, a
biochemistry professor at the University of Pennsylvania. Such
mitochondrial dysfunction inhibits apoptosis in malignant cells and
increases the invasive potential of cancer. Mitochondrial dysfunction
is also associated with conditions such as heart disease, diabetes,
obesity, blindness, deafness, kidney disease, and neurodegenerative
disorders, as well as with aging.
"[The respiratory stress-signaling] cascade culminates in the
activation of a large number of nuclear genes that affect various
cellular processes including cell metabolism, proliferation, and
apoptosis," says lead author Gopa Biswas, a researcher in Avadhani's
lab. "We have now established that TCDD alters cellular morphology and
physiology through a similar mechanism."
It is generally accepted that adverse effects of TCDD result from its
activation of the Ah receptor, with effects occurring at very low
exposures. In the presence of TCDD, the Ah receptor has been shown to
either induce or suppress the transcription of numerous genes that
have been linked with cancer development via changes in tumor
suppressor proteins, oncogenes, growth factors, and cell cycle
proteins, among other factors.
Mitochondrial dysfunction may entail a more fundamental mechanism. It
appears that TCDD-induced mitochondrial stress signaling in cancer
cells is propagated in part through the Ah receptor but also acts
through mechanisms that are independent of the Ah receptor, such as by
inducing protein kinase C and extracellular signal–regulated kinases.
"Our findings show that at subtoxic levels of ten to fifty nanomolar,
TCDD is sufficient to cause mitochondrial dysfunction and induce the
signaling cascade," says Avadhani. "These results raise concerns over
the adverse health implications of dioxins and PCBs even at very low
levels."
In both animal and human studies (notably epidemiologic analyses of
cancer rates following the 1976 industrial accident in Seveso, Italy),
TCDD exposure has increased cancer incidence and mortality at all
cancer sites rather than at a few specific sites. In 1997, the
International Agency for Research on Cancer upgraded TCDD to a Group 1
human carcinogen on the basis of mechanistic data. Considering
subsequent dose–response assessments for TCDD and cancer, Kyle
Steenland, a professor of environmental and occupational health at
Emory University, and colleagues argued in the September 2004 issue of
EHP that "TCDD exposure levels close to those in the general
population may be carcinogenic and argue for caution in setting the
upper ranges of long-term permissible exposure to dioxins."
The present study is limited in that it involved skeletal myoblasts,
not living organisms. "These findings are significant but
unfortunately provide no in vivo data showing tumor progression in
animals due to loss of mitochondrial function by TCDD," says Keshav K.
Singh, a cancer geneticist at Roswell Park Cancer Institute in
Buffalo, New York. "At a minimum, xenograft studies in mice are
needed." Avadhani now plans to study the precise mitochondrial targets
of different polychlorinated biphenyls (a related group of compounds)
that lead to reduced mitochondrial transcription and then examine the
implications of this pathway in tumor progression in vivo. He sees
possible implications for the prevention of breast, pancreatic, and
other endocrine cancers.
Recognition that the carcinogenic effects of environmental toxicants
may originate in disruption of mitochondrial biology could prove
important for the future development of cancer prevention and
treatment procedures related to TCDD and other dioxin exposures. "The
new findings suggest that the risk of cancer may be reduced by
avoiding or lowering exposure to environmental mitochondrial toxicants
as well as [possibly] by optimizing mitochondrial energy metabolism by
nutritional and medicinal means," says Egil Fosslien, a pathology
professor emeritus at the University of Illinois at Chicago |
|
|
| Back to top |
|
| |
|
Page 1 of 1
All times are GMT - 5 Hours
The time now is Fri Dec 05, 2008 8:04 am
|
|