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From: jay on 7 Aug 2008 16:22
> I actually think .. since dioxin results IN .. iron overload ..
> you should actually be pointing that OUT .. in your posts.
> Unless you don't understand the RESULT .. of .. dioxin .. ?
> Is that .. it ? You don't understand the iron levels .. ?
> There is increased IRON in the skin of people with lupus.
> Is there not .. ? It is being targeted with iron chelators .. ?
> Is it not .. ?
> The article posted points TO .. iron .. BEING .. involved IN skin
> necrosis when exposed to .. sunlight.
> Sooo .. one might assume you would start a thread about .. dioxin ..
> and explain how it causes .. iron overload.

Cellular functions such as growth, differentiation, detoxification,
death, etc are modulated by ligands binding with Aryl Hydrocarbon (Ah)
Receptors dispersed with in cell's cytoplasm. The ligand-AhR complex
translocate to the nucleus and alter cell's expression as encoded in
it's genes. Apparently the ligand is involved in determining cell's
response.

Persistent Organic Pollutants (ie PCBs, PAHs, HCA, dioxins) bind Ah
Receptors. TCDD, a dioxin, is the most potent activator of the Ah
Receptor. Among other things, TCDD causes cell's to manufacture
detoxification enzymes (ie CYP1A1, CYP1A2, CYP1B1) which require iron.
Thus TCDD exposure causes increase in cellular iron. The detox enzymes
aren't efficient at detoxifying TCDD. TCDD has a half life of about 10
year in humans. Pharacuetical companies frequently drop a drug like a
hot potato if it activates the AhR-mediated pathways.

Constantly enabling the AhR-mediated pathways produces a myriad of
effects including ROS and DNA damage. Sometimes TCDD amplifies the
detrimental effect of other POPs by detoxifying them to even more
toxic intermediates. There seems to be some evidence of cross talk
between AhR activation and COX and estrogen metabolism.

> Doesn't explain much up to .. what .. thirty years ago .. though.
> WHAT do you think was the cause of lupus before .. dioxin .. ?

The incomplete combustion of matter creates compounds that frequently
bind the Ah Receptor. This includes smoke from cigarettes, wood, coal;
charred meat, forest fires, volcanoes, etc. Due to differences in
genetics, one person eating charred meat may develop colon cancer,
while others may not.
From: jay on 7 Aug 2008 18:41
> Constantly enabling the AhR-mediated pathways produces
> a myriad of effects including ROS and DNA damage.
> Sometimes TCDD amplifies the detrimental effect of other POPs
> by detoxifying them to even more toxic intermediates.

Even while POPs in dietary fats has been reducing, the amount in
humans has been increasing due to TCDD's 10 year half life. Below is a
list of symptoms associated with dioxin exposure. It was created by
the Institute of Medicine (IOM) in 2007.

* Sufficient Evidence
Chloracne
Soft tissue sarcoma
Non-Hodgkin’s lymphoma
Hodgkin’s disease
Chronic lymphocytic leukaemia

*Limited/Suggestive Evidence
Respiratory cancers (larynx, trachea, lung, bronchus)
Prostate cancer
Multiple myeloma
Early-onset transient peripheral neuropathy
Porphyria cutanea tarda
Type 2 diabetes
Spina bifida (in offspring)
AL amyloidosis
Hypertension

*Inadequate/Insufficient Evidence
Hepatobiliary cancers
Cancers of oral cavity, pharynx or nasal cavity
Bone and joint cancer
Cancers of pleura, mediastinum, and other unspecified sites within
respiratory system and intrathoracic organs
Oesophageal cancer
Stomach cancer
Colorectal cancer
Pancreatic cancer
Cancers of reproductive organs (cervix, uterus, ovary, testis,
penis)Renal cancer
Bladder cancer
Leukaemia (other than CLL)
Melanoma
Non-melanoma skin cancers
Breast cancer
Cancers of brain and nervous system incl eye
Endocrine cancers
Cancers at other and unspecified sites
Infertility
Spontaneous abortion (other than for paternal TCDD exposure)
Birth defects (other than spina bifida)
Neonatal/infant death and stillbirth
Low birth weight
Childhood cancer in offspring incl AML
Neurobehavioural disorders
Movement disorders incl Parkinson’s disease and amyotrophic lateral
sclerosis
Chronic peripheral nervous system disorders
Gastrointestinal, metabolic and digestive disorders
Immune system disorders
Ischaemic heart disease
Circulatory disorders (other than hypertension and IHD)
Respiratory disorders
Endometriosis
Effects on thyroid homeostasis

*Limited/Suggestive Evidence of No Association
Spontaneous abortion and paternal TCDD exposure
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