[ RadSafe ] Re: Radiation Hormesis

John Jacobus crispy_bird at yahoo.com
Wed Dec 26 14:48:24 CST 2007

Dr. Long,
  Once again you confuse fact with speculation.  But that is not unusual for you.
  1.  It is interesting that 10 rem is the dose level at which no affects (good or bad) have found in human populations.  How does the late Dr. Luckey quantity this level with hormesis?  What benefits are there, if any?  My understand that acute affects can be mediated by "priming doses," but there is no benefits to subsequent cancer induction in animal populations.  If this a one-time dose, what if you receive 10 or 20 rem every year?  If he was such a proponent, what did he do to get his hormetic dose?  Or did he think that it was not important enough to receive any himself?  
  Dr. Luckey's work reminds me of Niels Bohr's old saw, that if you do not study physics, you are just collecting stamps.  Lots and lots of data do not make for good science.  It is the understanding of what are mechanisms of cause and effect that make for science.  I admire Dr. Luckey for collecting lots of data, but it has only been in the last decade with the new developments in biology that we are being to understand the science, and not the speculations, of his collection.
  What does you "toy" wrist alarm have to do with this discussion?  By the way you DO know what the difference is between 100 cGy and 100 cGy/hr?
  Again, there is no proof of the benefits of those exposed in the Taiwanese populations beyond the pure speculations of the Chen, Luan, etc paper, http://www.jpands.org/vol9no1/chen.pdf   (Why does the title end in a question mark?)  As noted on page 4 of the pdf "Accordingly, a detailed, official, government-sponsored epidemiologic study of these residents ought to be carried out to address uncertainties arising from the assumptions made in this study."
  2.  Of course, there were also the higher incidences of leukemia.  However, you may actually want to read the literature. http://www.rerf.or.jp/radefx/late_e/leukemia.html  But then why bother.  
  3.  I assume as a physician that you you understand the difference between a drug and a poison.  Many drugs, including aspirin, are toxic a high doses. If you wanted to protect yourself from arsenic poisoning, how much arsenic would you need to protect yourself? As I noted above, a priming dose may prevent or reduce the effects of an acute radiation dose, but there is no evidence that the effect is long lasting, despite what you believe.  Further, hormesis is just a new formulation of the discredited Arndt-Schulz rule http://en.wikipedia.org/wiki/Arndt-Schulz_rule
  4.  Again, as it the past, Dr. Pollycove was never a member of the NRC.  He served on an advisory committee.  However, facts are not really that important.  I think that it is important that you have a group to refer to that reinforce your beliefs.
  If you want to learn something new, maybe you should attend the NRCP's 2008 Annual Meeting, Low Dose and Low Dose-Rate Radiation Effects and Models, April 14 – 15, 2008, Bethesda North Marriott Hotel & Conference Center, 5701 Marinelli Road, North Bethesda, MD 20852
  5.  I have looked at this issue of hormesis and low dose, low-dose rate exposure for many years.  I find that your beliefs and ideas are wanting.  Maybe you should try to make the NCRP meeting.  
  I am pleased that you recognize the law of Bergonie and Tribondeau effect in CD133-expressed glial cells http://en.wikipedia.org/wiki/Radiosensitivity
  If you wish to reply, please do so off-list.  These are old and tired arguments, and we should not bore others.

howard long <hflong at pacbell.net> wrote:
          Merry Christmas, John Jacobus and Radsafers.
  1, What level?
  "Radiation Hormesis", TD Luckey, p36, shows supplemental radiation 
  curves with hormesis at 0 to about 20 cGy (~rem, rad etc) in an acute dose,
  the ZEP (zero equivalent point), after which there is more harm than good 
  (indicated by extensive animal and human data).
  Nukalert uses 100 cGy as the point of enough damage to get  away.
  The beneficial level of slow dose rate radiation seems much larger, as in Taiwan apartments. 
  2, Bomb survivors had lower mortality, except where GI symptoms ~ within a week.
  3, Poison. I take rat poison (coumadin) to slow clotting time, like millions of Americans.
   I also take sun baths (another radiation, "poison" in large dose) for vitamin D, bone strength, etc.
  4, Biological response to radiation, is well studied, reported in journals and presented to 
  Doctors for Disaster Preparedness by Pollycove 
  (a member of the Nuclear Regulatory Commission) and others. It is the stimulation of defenses 
  against oxygen disruption. It is many orders of magnitude greater than that caused by the radiation.
  Many presentations are available through www.ddponline.org  and www.oism.org/ddp 
  5, The flat earth question was raised because the earth does look flat - 
  unless one is willing to look from another perspective, like high above 
  (or the unexpectedly  better health of bomb survivors),
   or other science findings, like globe cicumnavigation (or the unexpected finding 
  that rats already overdosed with radiation survive better with additional radiation!)
  "In both cell culture and the brains of immunocompromised
mice, CD133-expressing glioma cells survive ionizing radiation in increased
proportions relative to most tumour cells, which lack CD133."
Is variability in cancer cell susceptibility unexpected? 
  Generally, slower growing cancers are less affected by radiotherapy.
  May this Good News supplement that brought to us 2,000 years ago.
  Howard Long
  ---- Original Message ----
From: John Jacobus <crispy_bird at yahoo.com>
To: howard long <hflong at pacbell.net>
Sent: Sunday, December 23, 2007 7:23:59 PM
Subject: Re: Mortality Rates best ConfirmBenefit from "hormesis"

    Then. at what level is "radiaton hormesis" beneficial? Did all the Atomic Bomb survivors have a benefit response?  You have failed to quantify the value.  Are you also implying that all cancers respond the same to same dose or dose rate of radiation? 
  By the way, which poisons would you take? Radiation is not a poison.  It is the deposition of energy that can lead to a chemical reaction, whick can lead to a biological response.  However, which responses occur? Cell death, cell recover, or cell mutation?
  What does you last paragraph have to do with the discussion?  

howard long <hflong at pacbell.net> wrote:
  The mortality rate would reflect any stimulation - or suppression of cancer.
  Whether bomb exposure or chronic radiation in humans or fast or slow rate in mice,
  hormesis is consistent in radiation as in sunshine as in allergens as in trace minerals.
  Small doses of poison actually benefit.
  Is the earth flat because viewed from a limited angle it appears so?
  Howard Long

  ----- Original Message ----
From: John Jacobus <crispy_bird at yahoo.com>
To: Dan W McCarn <hotgreenchile at gmail.com>; Bjorn Cedervall <bcradsafers at hotmail.com>; radsafe at radlab.nl
Sent: Saturday, December 22, 2007 2:46:15 PM
Subject: RE: [ RadSafe ] RE: Comment to "hormesis"

I find it interesting that those who foster the idea of "radiation hormesis" ignore the effects that are noted below, e.g., radiation eliciting a response that enhances the survival of cancer cells.  The deposition of energy from ionizing radiation certainly leads to may types of effects.  To cite one the "beneficial" effects and ignore harmful ones is clearly a case of cherry-picking the data that suit idea that one wants to foster.  The fact that those who oppose the use the radiation use the same selection process seems to be lost on many people.  
  We need to understand the various biological mechanisms the lead to the various celluar responses.  To blindly say that any radiation is good or bad is without scentific merit.  

Dan W McCarn <hotgreenchile at gmail.com> wrote:
  Comment on Hormesis, superficiality, and risk:

There was a very interesting letter in the magazine "Nature" last October
(on line) and December 2006 (in print) on the causative issues of why some
types of glioma stem cells (glioblastoma, a form of brain cancer) are quite
radiation resistant compared to normal brain cells. In the joint work of
Duke University and at M.D. Anderson, a glycoprotein was identified that
seemed to trigger radiation resistance. Their study (so far unpublished)
involved development of a vaccine that "blocked" this glycoprotein
preventing the glioma stem cells from developing radiation resistance. A
patient trial is underway. I am familiar with the trial at M.D. Anderson
because my roommate at Shell Oil was part of that study. Unfortunately,
"Uncle Bernie" recently succumbed to the disease at the age of 86.

Apparently there are some quite specific mechanisms that are activated by
radiation allowing preferential repair of DNA. In the words of the
researchers, this glycoprotein causes "preferential activation of the DNA
damage checkpoint response and an increase in DNA repair capacity". They
state further that "In both cell culture and the brains of immunocompromised
mice, CD133-expressing glioma cells survive ionizing radiation in increased
proportions relative to most tumour cells, which lack CD133."


I find it to be quite unfortunate that while cancer researchers seem to
embrace causative mechanisms for radiation resistance, there still appears
to be quite mixed and jaded response to the rather blunted word "Hormesis";
perhaps the word "radioresistance" might be more palliative.

While I am but a "mere" geologist, this article helped focus my
understanding that very specific cellular mechanisms account for what others
might call "Hormesis"; which appears to be too vague a term for many to be
able to "digest". In this way, I agree with Bjorn.

But to dismiss radioresistance out of hand, especially with specific models
being actively researched, seems perfectly absurd.

The abstract follows.

Dan ii

Dan W. McCarn, Geologist; 3118 Pebble Lake Drive; Sugar Land, TX 77479; USA
Cell: +1-505-710-3600; Home: +1-281-903-7667; Fax: +1-713-241-1012; Office:
HotGreenChile at gmail.com, Dan.McCarn at shell.com 

Nature 444, 756-760 (7 December 2006) | doi:10.1038/nature05236; Received 1
June 2006; Accepted 7 September 2006; Published online 18 October 2006

Glioma stem cells promote radioresistance by preferential activation of the
DNA damage response
Shideng Bao1,2, Qiulian Wu1,2, Roger E. McLendon2,3, Yueling Hao1,2, Qing
Shi1,2, Anita B. Hjelmeland1,2, Mark W. Dewhirst4, Darell D. Bigner2,3 and
Jeremy N. Rich1,2,5,6

Department of Surgery,
Preston Robert Tisch Brain Tumor Center,
Department of Pathology,
Department of Radiation Oncology,
Department of Medicine, and,
Department of Neurobiology, Duke University Medical Center, Durham, North
Carolina 27710, USA 
Correspondence to: Jeremy N. Rich1,2,5,6 Correspondence and requests for
materials should be addressed to J.N.R. (Email: rich0001 at mc.duke.edu).

Top of pageIonizing radiation represents the most effective therapy for
glioblastoma (World Health Organization grade IV glioma), one of the most
lethal human malignancies1, but radiotherapy remains only palliative2
because of radioresistance. The mechanisms underlying tumour radioresistance
have remained elusive. Here we show that cancer stem cells contribute to
glioma radioresistance through preferential activation of the DNA damage
checkpoint response and an increase in DNA repair capacity. The fraction of
tumour cells expressing CD133 (Prominin-1), a marker for both neural stem
cells and brain cancer stem cells3, 4, 5, 6, is enriched after radiation in
gliomas. In both cell culture and the brains of immunocompromised mice,
CD133-expressing glioma cells survive ionizing radiation in increased
proportions relative to most tumour cells, which lack CD133.
CD133-expressing tumour cells isolated from both human glioma xenografts and
primary patient glioblastoma specimens preferentially activate the DNA
damage checkpoint in response to radiation, and repair radiation-induced DNA
damage more effectively than CD133-negative tumour cells. In addition, the
radioresistance of CD133-positive glioma stem cells can be reversed with a
specific inhibitor of the Chk1 and Chk2 checkpoint kinases. Our results
suggest that CD133-positive tumour cells represent the cellular population
that confers glioma radioresistance and could be the source of tumour
recurrence after radiation. Targeting DNA damage checkpoint response in
cancer stem cells may overcome this radioresistance and provide a
therapeutic model for malignant brain cancers.

-----Original Message-----
From: radsafe-bounces at radlab.nl [mailto:radsafe-bounces at radlab.nl] On Behalf
Of Bjorn Cedervall
Sent: Saturday, December 15, 2007 10:31 PM
To: radsafe at radlab.nl
Subject: [ RadSafe ] RE: Comment to "hormesis"

Hormesis is a mix of many different phenomena. Therefore the concept causes
confusion unless each phenomenon is analyzed and interpreted separately:
adaptive response (priming, by-stander effects, genomic instability,
induction of radical scavengers & repair enzymes etc), stress mechanisms,
evolution of evolvability (including tuning of mutation rates), natural
(statistical) selection against those least fit, the individual vs. the gene
pool of the same species etc, interpretation of what is good/bad for an
individual vs. the corresponding population and so on. This boils down to:

The concept "hormesis" gives no help in the understanding of radiation
biology and all its subtopics can be discussed under headings such as those
just mentioned (part of evolutionary biology). It was perhaps OK to lump all
the different biological phenomena ("radiation is beneficial"...) 30 to 70
years ago but today when we know so much more about radiobiological
mechanisms we do not have any use for that word.

Hormesis is often referred to in a superficial way like "radiation is good
for you" which basically only can hurt the nuclear industry because the
business may be perceived as being driven by narrow minded cynical risk
takers which, as most of us know, is far from the dominating attitude.

My personal ideas only,

Bjorn Cedervall bcradsafers at hotmail.com
PhD, Associate Professor (Medical Radiation Biology, Karolinska Institutet)
MSc (Theoretical Chemistry: Nuclear chemistry & biochemistry, Royal
Institute of Technology)
Radiology specialist (Nuclear power safety) - have now been in this field
for 24 years.

"If history teaches any lesson it is that no nation has an inherent right to greatness.  Greatness has to be earned and continually re-earned."
- Norman Augustine, Chairman of the National Academies Committee 

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