[ RadSafe ] cancer is the result of defective tissue/immunecontrol

[Muckerheide, Jim (CDA)]

That's great John.  

You see that radiation-induced cancer is NOT caused by DNA damage.

Also, that the biological responses of low vs. high doses are different (essentially "opposite").  They are discontinuous in health effects (as low as 20-30 rem for acute dose ratse - for some cancers, but then not usually for total-cancers - so is that significant "health effect")?  

At the low dose rates, the biological responses are those that explicitly stimulate factors that perform/enhance "error-free" repair, including immune cells and functions, and other damage response and repair mechanisms, especially key enzymes.  At higher doses, different genes and other factors respond, with opposite responses (stimulated vs, suppressed, or vice versa) by a subset of genes and other factors.

Cancer is the result of failure to repair damage in tissues, not of damaged cells (much less DNA), of which moderate to high doses make a small contribution to normal metabolic damage, including double strand breaks.

This was the basis of the letter from the DOE Director of the Office of Science to the President of the NAS stating that the BEIR VII Committee had failed to take into account the current knowledge of radiation effects. Indeed, BEIR VII just regurgitated much irrelevant and discredited data, while obfuscating some relevant data, and simply ignoring the voluminous actual data, as always, since 1935-36. (We can identify more than 3000 data sources, since 1896, while there are essentially NO confirmed sources supporting the LNT.  There are few, perhaps less than a dozen, nominally relevant, confirmed, results that are claimed to support the LNT.  These are like Alice Stewart's claim that fetal x-rays caused increases in childhood cancer, which is of dubious significance even if it were true. But this was from interview recollections of x-rays which are subject to bias by people
with adverse consequences vs. those who did not. This is claimed to be confirmed by McMahon in Boston, with a similarly uncertain study.  However, more definitive studies. e.g., a cohort in Chicago in which all women were x-rayed without medical indication to bias selection "for cause" which would clearly tend to refute low doses as a possible cause of health effects. We sent several hundred refs and made a presentation, as did Ed Calabrese, without any substantial assessment of the data.) 

These committees are the equivalent of people who would claim that apples can fall UP, and claim that 'we really don't know what makes gravity work' so we can't really know that they don't just because we haven't seen them.  But they would "recommend" putting nets over all the orchards in order to protect us from losing apples until the research can be certain one way or the other.  

Of course, they would then claim that apples falling up may be "tunneling" through the net "barrier."  They could say, with a straight face, that it was because of DNA damage - wait, that is, "it's because the core of the earth is magnetic, and some apple seeds in the apple core (which are also magnetic, which make the apple fall) can change polarity, causing the apple to be ejected into outer space so fast that it is never seen." Of course they would be working for the net-makers who use these researchers to get the king to provide more funding for "research"and radiation protection - that is, "netting the orchards" with thousands of square miles of nets (with public funds to "protect society" from the possibility of losing apples - with the danger that some apples could come back to earth with enough energy to kill somebody :-). 

The government has done this since FDA got a "scientist" to write a report, which they got funded through the NAS in 1935-36, to claim that there was no stimulation by low doses. (This primarily addressed plants, since she was a botanist!? She had conducted large experiments in the early '30s that she claimed had failed to see stimulation - Edna Johnson at U. Colo.) She  did not apply the work of her own thesis advisor (Duggar, at U. Wisc.) or substantial work that had gone on since before 1900, with a major compilation of the data in 1908 (by Gager, 2 papers) which was adopted as still the definitive study on plants by Richards in a substantial cover article in "Science," Sep 3, 1915, on "the physiological effects of radiation" in which low vs. high doses were addressed.

Murphy, and others, showed in testing immune response for suppressing cancer (e.g., in the PNAS, 1920, for physical treatments, i.e., heat and radiation) that, for radiation, 'at higher doses lymphocytes were suppressed compared to controls' (and cancers increased), but 'when the dose was further reduced, suddenly the lymphocytes were stimulated compared to controls' (which caused cancer to be REDUCED compared to controls, with irradiation either before or after injection of cancer cells). 

In a later paper, another author (blank-at-the-moment, 1925, J. Exp. Med. :-) stated in his first paragraph that the claim that the effects of low doses are simply a lesser response to the effects at high doses had been shown (by Murphy and others) to be in error by showing that the effects at low doses are different/opposite, and discontinuous, compared to the effects at high doses.

And, of course, this is what recent microarray analysis of thousands of genes and other factors shows (although without the animals/health effects results, carefully reducing the ability to make subsantial conclusions on health effects), plus the thousands of experiments, including that original work at Rockefeller University, and the work of hundreds of experimenters over the intervening decades. This especially includes Liu at the Norman Bethune Medical School (now incorporated in Jilin University) in Changchun China. (He was formerly the university president there, and he was a researcher in the premier AEC radiobiology research program at Rochester.) And now the work by several experimenters in Liu's lab, and in labs supported by the DOE Low Dose Research Program.  

Of course, such results in the past have simply, and continuously, been ignored by the closed cabal of well-funded/rewarded reviewers that control the radiation research funding and academic and government appointments, who write the BEIR Reports, the NCRP and ICRP reports, fill agency Advisory Committees and contracts for "studies" of radiation health effects "consequences," etc.  

Of course, this excludes the researchers doing the substantial immunologically-whole animal low-dose research (who can even be on some committees, but fear retribution by speaking out too much, and/or are seeking advancement in their "chosen profession.")  Norm Frigerio told me around 1978 that "We no longer get 'the best and the brightest' coming into radiobiology research. Most of them see what it takes to succeed while doing graduate research, and decide to do something else with their interests and skills. And we get the people who see what it takes to succeed (in the AEC-funded programs), and (unfortunately) chose to 'play the game,' to make it their career.

As I've reported before, I had the (good?, or dubious?) fortune, following a meeting when we were addressing AEC Part 50 App D and App I regulations, to sit in on a discussion between a senior AEC official and a senior Oak Ridge scientist, with my boss, a recently retired former AEC official. These guys shared experiences about people at Oak Ridge (and elsewhere) "who were given other things to do" when they wanted to pursue the beneficial effects of low dose radiation. A 1961 (May?) paper by Hugh Henry (who was at Oak Ridge at the time) in the J, of the Amer. Med. Assoc. Art Upton, at Oak Ridge, tried to keep him from publishing the paper, and the editor at JAMA, in correspondence with Marshall Brucer, said he had to decide to "take on" those arrogant "people" to decide to publish the paper "anyway."

The results refuting the LNT had especially been demonstrated in work during the Manahattan Project, under Bob Stone, i.e., by Miriam Finkle, Egon Lorenz, and others.  See Lorenz' work in the voluminous 1954 McGraw-Hill series on Manhattan Project science (Vol. 22F? or some such letter? :-).  See also his late-'40s and 1950, etc., papers where he had already obfuscated those results.  He had also eliminated the lower doses in similar post-war work. He dropped the 0.044 r/day group, starting at 0.11 r/day - 40 r/year.  This also resulted in longer life spans, but tis was ignored by drawing a straight line through the data.  There were lifetime doses up to 2,000 r and 2,500 r, with no adverse health effects, generally normal litters, and longer mean lifespans. Nevertheless, he stated in papers that 'any dose is likely to have adverse effects.' 

Lorenz worked for NCI.  Suppressing the low-dose radiation health effects data was originally a medically-driven cause. It was not radiation protection-driven. This was done to limit competition for the drug companies, especially for penicillin after the war. That's why FDA was the original agency suppressing the data starting in the 1930s, using the 1932 death of Eben Byers. Byers had been ingesting about 10 million pCi/day of Ra-226-equivalent (3 vials/day with 0.1 mCi of both Ra-226 and Ra-228) for about 3 years.  He started when he was 51, with great initial invigoration) compared to EPA's 5 pCi/L, 4 mrem per year!? (say 2,000 pCi/year) ingestion limits.  But of course, having gotten Congressional authority to control radium, they didn't follow the thousands of people who had been ingesting radium, even with the then well-known radium dial painter ingestion experience, nor did they limit its use and/or body-burden, they just required that it had to be applied by doctors. Their initial "problem" was solved.

It was also influenced by the arguments over the bomb, first to keep it from being turned over to the Army, then anti-bomb people on phony 'hazards' of above-ground testing.)

Oh well, it's late.  I wasn't planning to take the time for this :-)  but it's been a while since I've addressed these issues. :-)  I intended to link to some of these various data sources on our web site, but I'll pass at the moment. :-)  Let me know if there are specific sources that you want to see if we have on the site.

Regards, Jim Muckerheide


-----Original Message-----
From:	radsafe-bounces at radlab.nl on behalf of John Jacobus
Sent:	Thu 6/29/2006 5:19 PM
To:	Rainer.Facius at dlr.de; radsafe at radlab.nl
Cc:	
Subject:	Re: [ RadSafe ] cancer is the result of defective tissue/immunecontrol

Rainer,
As you note, at least in murine gastrointestinal
cancer (sic) this is true.  However, I do not think
you can say this about other cancers.  I guess you
could, but do you think all cancers are due to
defective tissue/immune control?  It is a question of
recognition of "self," e.g., cancers are recognized as
normal tissues, which they are to the immune system.

--- Rainer.Facius at dlr.de wrote:

> For those who always knew that (at least murine
> gastrointestinal) cancer is the result of defective
> tissue/immune control.
> 
> "The results support the concept that cancer, as an
> outcome, reflects the loss of the normal
> communication between the cellular constituents of a
> given organ8, and indicate that Smad4-deficient T
> cells ultimately send the wrong message to their
> stromal and epithelial neighbours."
> 
>
http://www.nature.com/nature/journal/v441/n7096/full/nature04846.html
> 
> 
> 
> Regards, Rainer
> 
> Dr. Rainer Facius
> German Aerospace Center
> Institute of Aerospace Medicine
> Linder Hoehe
> 51147 Koeln
> GERMANY
> Voice: +49 2203 601 3147 or 3150
> FAX:   +49 2203 61970
> 
> Nature 441, 1015-1019 (22 June 2006) |
> doi:10.1038/nature04846; Received 9 February 2006;
> Accepted 28 April 2006
> 
> Byung-Gyu Kim1, Cuiling Li2, Wenhui Qiao2, Mizuko
> Mamura1, Barbara Kasperczak3, Miriam Anver3,
> Lawrence Wolfraim1, Suntaek Hong1, Elizabeth
> Mushinski4, Michael Potter4, Seong-Jin Kim1,
> Xin-Yuan Fu5, Chuxia Deng2 and John J. Letterio1
> 
> Smad4 signalling in T cells is required for
> suppression of gastrointestinal cancer
> 
> Abstract
> 
> SMAD4 (MAD homologue 4 (Drosophila)), also known as
> DPC4 (deleted in pancreatic cancer), is a tumour
> suppressor gene that encodes a central mediator of
> transforming growth factor- signalling1, 2, 3, 4.
> Germline mutations in SMAD4 are found in over 50% of
> patients with familial juvenile polyposis, an
> autosomal dominant disorder characterized by
> predisposition to hamartomatous polyps and
> gastrointestinal cancer5, 6. Dense inflammatory cell
> infiltrates underlay grossly normal appearing,
> non-polypoid colonic and gastric mucosa of patients
> with familial juvenile polyposis7. This prominent
> stromal component suggests that loss of
> SMAD4-dependent signalling in cells within the
> epithelial microenvironment has an important role in
> the evolution of intestinal tumorigenesis in this
> syndrome. Here we show that selective loss of
> Smad4-dependent signalling in T cells leads to
> spontaneous epithelial cancers throughout the
> gastrointestinal tract in mice, whereas
> epithelial-specific deletion of the Smad4 gene does
> not. Tumours arising within the colon, rectum,
> duodenum, stomach and oral cavity are stroma-rich
> with dense plasma cell infiltrates. Smad4-/- T cells
> produce abundant TH2-type cytokines including
> interleukin (IL)-5, IL-6 and IL-13, known mediators
> of plasma cell and stromal expansion. The results
> support the concept that cancer, as an outcome,
> reflects the loss of the normal communication
> between the cellular constituents of a given organ8,
> and indicate that Smad4-deficient T cells ultimately
> send the wrong message to their stromal and
> epithelial neighbours.
> . . .

+++++++++++++++++++
"You get a lot more authority when the workforce doesn't think it's amateur hour on the top floor."
GEN. MICHAEL V. HAYDEN, President Bush's nominee for C.I.A. director.

-- John
John Jacobus, MS
Certified Health Physicist
e-mail:  crispy_bird at yahoo.com

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