The ultimate Hormesis experiment

[sandlapper]

This comes from a questionable source but I can't find anything that refutes it.

http://www.sepp.org/weekwas/2003/Jul26.htm

"At the ongoing 48th Annual Meeting of the Health Physics Society in San Diego, I encountered poster paper P.78 entitled "The Beneficial Health Effects of Chronic Radiation Experienced in the Incident of Co-60 Contaminated Apartments in Taiwan." This paper has 14 authors, all associated with nuclear and radiation protection organizations in Taiwan, including one from the National Taiwan University. The lead authors are W.L. Chen and Y.C. Luan, Nuclear Sciences and Technology Association, 4th F, W. 245, Sec. 3, Roosevelt Road, Taipei, Taiwan, ROC."

<snip>

"The authors compared the approximately 10,000 people in this study with published cancer mortality statistics and reported an expected incidence of about 217 cases of cancer during the study period. The actual number of cases found was only 7. This demonstrated about a 97% reduction in cancer incidence for people living in the high-radiation environment of these contaminated apartments. They found a similar reduction in "genetic defects". The authors could not find any obvious confounding factors associated with their study.
The abstract of this paper is found in a recent published HPS Journal Supplement. You can write to the authors to get the whole paper."

[pw]

1. Obvious confounders

Include bad diagnosis and followup and bad matching to control groups. For example, we don't know what the overall mortality was among those 10,000 people (you're going to get a lot fewer cancer deaths if people are dying of heart attacks or road accidents), or how well the average exposure to tobacco smoke, pollution or other chemical carcinogens matches that of the population at large. We don't know how many people in the study were lost to followup at some point (it's easy to claim fewer deaths if you lose track of people, say when they move out and go to a hospital). We don't know how well the age and occupational profiles match those of the population at large. (Heck, we don't even know the source of the "published cancer mortality statistics".) We don't even know how much time people spent in the "high-radiation environment" in question.

The "high-radiation" environment, by the way, appears to average about twice the international standard occupational exposure limit, which is also about twice the maximum background level anyone lives with. (About 10x the typical north american baclground level.) Some people appear to have accumulated exposures more like 100x typical background, but the report doesn't say anything about the cancer statistics for that subgroup.

[dfong63]

2. that says a lot

The authors could not find any obvious confounding factors associated with their study.

[sandlapper]

3. Do you have the paper?

I've contacted the authors but haven't heard from them. The summary at the SEPP site indicated that the authors had investigated for confounding influences and found none. You've apparently found some reasopn to question their thoroughness and I'd really like to know what it is. Intuitively hormesis seems to be a logical defense mechanism for an organism to develop if it has to survive in a moderate radiation environment.

[enki23]

4. from the end of the abstract:

"...The hormetic health effects of chronic radiation might also occur in other substances, such as toxic chemicals and microorganisms, it might conclude that any toxic substances received in low dose rate is always beneficial to humanity even in quite amount dose."


tell me that's just a really, really bad translation. hormesis is a real phenomenon, as common sense might dictate, but they sound like teenagers babbling about getting laid for the first time. did they just get around to reading about it in their biology textbook, or what?

this paper doesn't seem to have actually been *published* anywhere. it was presented at a conference, but it hasn't been peer reviewed. assuming this is legit for the moment, there may, or not be real evidence of hormesis in this case. there *is* some evidence that single low doses of radiation can stimulate IgG production, but it isn't until the initial toxic effects have subsided that possible beneficial effects start to show up. with chronic exposure, it seems questionable that would ever happen.

but what *really* gets me is their assertion that "any toxic substances received in low dose rate is always beneficial..." is either a completely botched translation, or the author is an imbecile. claiming hormesis in *every* case is worse than claiming it in none.

[sandlapper]

5. Why then does Radiation Physics use LNT?

That is what has bothered me for sometime. The dosimetry recommendations of the EPA and DoE all assume that there is no minimum threshold for radiation damage, essentially denying hormesis. Radiation biologists in the "main stream" seem to have bought into this.

[enki23]

7. because there *is* no threshhold for damage

a single "radioactive" particle--alpha, beta, photon, whatever--will do damage if it hits a target. (actually, they usually hit water and create reactive oxygen species which then often go on to damage dna.) any given particle, of the same type and energy, has the same basic chance to hit an important target. there is no threshhold, because mechanistically it makes no sense. of course, that's the case for most toxins. but in the case of cancer, it gets a lot more tricky. most toxins have to damage a lot of cells before their effects are significant. cancer, theoretically, only takes one. statistically* there is a threshhold below which you get diminishing returns for the exposure-reducing efforts required to lower it further, yes. the difficult question, then, is what it's always been: what level is that?

while the increased risk of cancer is small for any small increase in radiation dose, cancer is a very nasty outcome. risk might be small, but the potential hazard is very large. this is the sort of reasoning that went into legislation like the delaney clause, which basically says that you cannot add anything to food, drugs, or cosmetics at all that is known to cause cancer in humans or animals.

anyway, the point i'm getting around to is this: these substances do not have a "real" threshold, as such. that is, unless you're talking about single hits (neoplasias are the result of multiple mutations. a single damaging event couldn't cause cancer by itself, unless the cell were already somehow compromised.)

with this idea of hormesis, you have to keep in mind that the potential beneficial effects and the potential damaging effects are *simultaneous.* it's not like the bad effects only happen at higher doses, and the beneficial effects happen only at low doses. the problem is that at higher doses (depending on what you mean by "higher") the beneficial effects--assuming such effects really exist to any appreciable extent--are overshadowed by the inherent toxicity. the studies i've seen (i admit i've only looked at it briefly) have found these potentially beneficial effects only in the case of single low doses. there was a delay, the lenghth of which depended on the dose, before the "beneficial" effects showed up. this is because the toxic effects had to fade first. and there is no guarantee that there is *any* level at which any beneficial effects would outweigh the increased risk. they *might*. they also might not, and it might be really damned difficult to tell for sure. when you're not sure about something like cancer, you tend to err on the side of caution.

also... it seems to me that adding to your background radiation dose is not adding a "single" low dose. there is almost no conceivable environmental radiation source which would supply these periodic low doses, unless perhaps you'd get some accurately calibrated dose with your morning coffee, on your way to work, or whatever. or if the range of these doses were fairly wide, encompassing doses significantly greater than those we already receive.

[treepig]

8. a comment on environmental radiation sources

there is information in the "Uranium, burning coal, and environmental hazards" thread ( http://www.democraticunderground.com/discuss/duboard.php?az=show_topic&forum=115&topic_id=169&mesg_id=169 ) that pertains to your statement:

"there is almost no conceivable environmental radiation source which would supply these periodic low doses, unless perhaps you'd get some accurately calibrated dose with your morning coffee, on your way to work, or whatever."

particular, lkinsale supplies the following information in post #1:

"As an exploration geologist, my problem was often distinguishing significant (to me) levels of radioactivity from the high background. There is indeed a lot of natural background radioactivity that few people realize. Some examples:

-Grand Central Station (because it is built of granite) has a higher level of radioactivity than is allowed around nuclear power plants.

-A cross-country plane flight exposes the passengers to levels of radioactivity that are higher than a chest x-ray (At least an early '80s chest x-ray. The xrays may be lower now, the plane flights are not--probably higher with the changes in ozone.)

-Radon gas is a common natural emission from some soils and water. It can accumulate in homes to high levels of exposure. It produces highly radioactive daughters in a gaseous state which can be breathed into the lungs.

-Burning wood emits radioactive components, because the trees have accumulated radioactive elements from the soil which are released in smoke and ash.

-During my exploration days, I came across several instances where people had built fireplaces or summer houses using local materials that measured as very radioactive on my equipment. This is probably more common than realized."

therefore, if you regularly (or sporadically) commute through grand central station, fly, breathe radon in your basement (and I'm sure there's a lot more examples) there actually is a reasonable chance that you would be exposed to 'hormesis' levels of radiation from daily activities.

[treepig]

9. a comment on the threshold for damage

you present many good points concerning the biological effects of radiation and how it is thought to cause cancer. however, i believe you overlook a key issue, namely, that the 'threshold for damage' is less important than the ability to repair the damage that results from radiation.

in the case of cancer, DNA is the cellular component of interest - and DNA suffers a huge amount of damage from normal cellular metabolism. to simplify things, oxidation of the foods we eat is not 100% efficient, instead the reactive oxygen species you speak of resulting from radiation also occur on a day to day basis from the normal metabolic activities of a cell. according to work from the laboratory of bruce ames at the university of california (berkeley), these metabolic byproducts (and other agents) damage the DNA in each cell at between 50,000 and 250,000 sites every day.

this high level of damage is usually not a problem because cells contain many DNA-repair enzymes that 'fix' the DNA. in bacteria, radiation hormesis is a proven fact - when exposed to radiation (and other DNA-damaging agents), the cutely named 'SOS response' occurs wherein cellular levels of DNA repair enzymes are dramatically upregulated. the potential for hormesis in people is less clear (i.e., there is conflicting evidence whether DNA repair enzymes are upregulated or not) - however, there is almost certainly a threshold beneath which exogenous radiation provides so little of an additional cellular damage load (compared to what occurs naturally) as to be inconsequential. to give one example, before DU1 met it's demise i posted information there that the maximum DNA damage that could be inflicted on a cell by an inhaled particle of depleted uranium is 2.2 sites per day. considering the 'background' levels of 50,000 to 250,000 sites of damage a day, it is not reasonable to be concerned about the new levels of damage, i.e., 50,002 to 250,002 sites of damage per day (in fact, statistically speaking, the levels of damage have not increased).

ok, having hopefully made the point that a threshold for the repair of damage is the issue at stake (and not merely damage itself), the issue of hormesis remains fuzzy. However, i just recently came across a study where a cellular mechanism for such hormesis is hinted at:

Journal of Nutrition. 2003 Aug;133(8):2543-8.

Title: Zinc deficiency induces oxidative DNA damage and increases p53 expression in human lung fibroblasts.

This study examined the effects of zinc deficiency on oxidative stress, DNA damage and the expression of DNA repair enzymes in primary human lung fibroblasts by the use of DNA microarrays and functional assays. . . . . Zinc deficiency in cells caused an increase in oxidant production (dichlorofluoroscein fluorescence) and a significant induction of single-strand breaks (Comet assay) and p53 protein expression (Western blot analysis).


so what happens here is that DNA damage (of the type also caused by radiation) significantly increases the amount of p53 in a cell. this result is significant because p53, a protein that has been called 'the guardian of the genome' is able to detect DNA damage and then trigger apoptosis (programmed cell death). in this manner, a damaged cell, instead of going on to become cancerous instead harmlessly dies and is removed from the body. perhaps passing through grand central station on your daily commute (refering to the post above) will increase your p53 level, then when you fly (egad, radiation exposure on the flight) to colorado (ugh, more radiation due to the high altitude) and breath in the radiation-filled campfire smoke - this combined assault on your DNA will not cause cancer, instead your enhance p53 levels will quietly do away with any cells that become irrevocably damaged.

[enki23]

10. sure. but the data just doesn't exist to support it (yet?)

that's the problem for *every* side of the radiation question. there is very little statistically significant data available for the lowest end of the dose-response curve. there seem to be some studies which point toward a hormesis style dose-response curve. but significant reproducible evidence just isn't there, at least yet,that any such possible stimulation of repair mechanisms (at any given dosage) would outweigh the increased risk from the harmful effects themselves.

as one researcher has suggested (ken mossman, "radiation risks and linearity: sound science?"):

you'd need to establish a causal relationship between radiation dosage and any given repair mechanism stimulation (would require significant evidence of correlation, reproducibility, etc.)

you'd have to demonstrate that stimulatory effect has a dose-response relationship with radiation exposure.

you'd have to show that the stimulatory effect was significant enough, at least at some level, to outweigh the increased toxicity

none of that exists yet.

so far as the linear model goes, i'd agree that it's probably not very useful on the low end. most would, i suppose. i suspect it's mostly kept around because 1) it's entrenched and 2) it's conservative. we just don't don't like to mess with cancer.

[treepig]

11. to be clear,

my post was less intended to tout the possible hormetic effects of radiation than to argue against the prevalent paranoia about all things linked to radiation. for example, i recently had a conversation with someone who was demanding long prison terms for anyone who introduced so much as ‘one molecule of radiation’ into the environment where an unsuspecting citizen might be exposed. it’s pretty much hopeless to present rational arguments to this type of person along the lines of “let’s assess the risk of the artificial radiation in terms of the ubiquitous radiation we’re exposed to everyday. . . btw, an interesting website for such information is at http://www.physics.isu.edu/radinf/natural.htm ).


having said that, i completely agree that it would be foolish to go out of one’s way in order to deliberately expose oneself to radiation for cancer prevention purposes. on the other hand, nature seems to have provided plenty of opportunities to achieve some level of radiation hormesis just by going about your routine activities. anecdotally, in the first half of the 20th century the public was exposed to radiation that would be unthinkable today (for example, x-rays to check the fit of a shoe, uranium-glazed dinnerware, radium glow-in-the-dark instrument panels) and overall cancer rates were much lower (of course, workers such as the women who painted the radium onto the instrument panels, were severely affected).

perhaps somewhat related is an epidemiological study (which, almost by definition tend not to be definitive) studying the effects of EMF (powerline, cell phone, etc) exposure. what this study found upon examination of 200-odd types of cancer was that EMF exposure statistically increased the occurrence of 3 types of cancer but decreased 17 types of cancer (with 90% of the types being unaffected). if these findings are accurate, they raise some interesting dilemmas – when considering the overall health of everyone, exposure would be a good thing because there’d be less cancer. however, in real life the people who didn’t the 17 types of reduced cancer would never realize their good fortune whereas the people who were afflicted with one of the 3 types of increased cancer would be outraged and sue the responsible electrical utility or cell phone maker (once again, the studies are far from definitive and never stand up in a court of law – but it’s an interesting thing to think about).

[treepig]

13. newly emerging information of relevance to thresholds

can be found in abstracts presented here (ok, it's actually 1 1/2 years old, but it's new to me and this thread):

http://www.ornl.gov/TechResources/Human_Genome/publicat/02santa/lowdose_infra.html

(unfortunately, it doesn't appear the full work has been published, or the research is in a preliminary stage, so the following information should be taken with a grain of salt, so to speak)

here's one of the several abstracts:

Efforts to sequence the human genome and to make this information available to the scientific community are already paying great dividends. New genomics data and technology make it possible to address important societal issues in biology, medicine, and even in health risk. One application has been to apply these techniques to determine the cellular and molecular responses induced by low doses of ionizing radiation. Before the genome project, it was not possible to determine biological responses to very low levels of ionizing radiation (below about 0.10 Gy). The Low Dose Radiation Research Program funded by the DOE Office of Biological and Environmental Research was made possible by the merging of new technological developments with the genome research. The overall goal of this program is to provide a sound scientific basis for radiation protection standards. The program has been in place for just over three years and is currently funding 54 projects. There have already been several major breakthroughs resulting in a re-evaluation of basic radiation paradigms on which current radiation risk standards were set. These breakthroughs are a direct result of the gene chip and sequencing technology generated by the genome program. There is now evidence that cells do not require a direct “hit” to exhibit changes in gene expression, gene mutation and chromosome damage, but may also respond if a neighbor cell is irradiated, a phenomenon called the “bystander” effects. Such observations make it necessary for us to re-evaluate the effective biological target size for radiation and the significance of the long held “hit theory” of radiation biology. It has also been demonstrated that exposure of the matrix on which cells grow can change both the pattern of gene expression and the cells phenotype to result in cell transformation without direct induction of mutations. Therefore, the relative role of mutations and gene expression in cancer induction must be redefined. This may result in potential impacts on the basic linear-no-threshold hypothesis that is used in standard setting. Finally, low dose studies have demonstrated that the pattern and type of genes expressed after low doses of radiation are different from those observed after higher doses. Research has also shown that these patterns of gene expression influence many important genes involved in repair of DNA damage, as well as in programmed cell death (apoptosis). Results of recent studies suggest that low doses of radiation may decrease the level of spontaneous cell transformation resulting in another expression of the “adaptive response”. Without the advances in genomics most of these observations would not have been possible. Their impact on radiation risk and standards remains to be determined. However, the research from the Low Dose Program will provide a sound scientific basis for radiation risks. Continued application of new equipment, methods and techniques will be important in addressing many important scientific and societal needs.

other abstracts describe specific studies where low doses of radiation were found to affect the expression of hundreds of genes - the next step is to figure out if these are protective or harmful genes.

[treepig]

6. just in case readers of this thread missed it

i'll take the liberty of copying this post to here:

*********************************

Is it conceivable that we have an "immune system" which responds to low-level long term doses of radiation?

It's called "radiation hormesis". Here's a quick glance at it:

http://www.angelfire.com/mo/radioadaptive/inthorm.html

********************************

note that this information was originally supplied in this thread

http://www.democraticunderground.com/discuss/duboard.php?az=show_topic&forum=115&topic_id=169&mesg_id=169

by JonasQuinn in post #7

note to moderator: if it is illegal to re-post information in this way, please delete this post.

[HungryLoser]

12. I just want to say, in all sincerety,

you guys are pretty freakin smart! I just learned something, and it didn't hurt my head or make me mad. How refreshing for a change.
I just had to say that. (I'm also really attracted to honestly intelligent people, I'm not that smart.)

[TrogL]

17. don't put yourself down

If you managed to wade through all that - you're not entirely stupid.

Reading theads like this is what makes me love DU. Try and find this kind of content on Free Republic, or anyplace else for that matter.

[treepig]

14. a relevant article in the september 2003 scientific american

<a href="http://www.sciam.com/article.cfm?articleID=00053833-173D-1F30-9AD380A84189F2D7&ref=sciam">Scientific American: Nietzsche's Toxicology < HORMESIS ></a><br>Whatever doesn't kill you might make you stronger

If dioxin and ionizing radiation cause cancer, then it stands to reason that less exposure to them should improve public health. If mercury, lead and PCBs impair intellectual development, then less should be more. But a growing body of data suggests that environmental contaminants may not always be poisonous--they may actually be good for you at low levels.

Called hormesis, this phenomenon appears to be primarily an adaptive response to stress, says toxicologist Edward J. Calabrese of the University of Massachusetts at Amherst. The stress triggers cellular repair and maintenance systems. A modest amount of overcompensation then produces the low-dose effect, which is often beneficial....continued at Scientific American Digital

on edit - the link doesn't provide the entire article (sorry - think you have to pay for it)

[seventhson]

15. It is still bullshit

who DO you work for?

Ionizing radiation is GOOD for you?

The title of the article is "What doesn't KILL you may make you stronger>"

My children are ill due to people like you.

[treepig]

16. always nice to get well reasoned, intellectually compelling arguments

i work for the johns hopkins university (a fact that has little to do with the information presented in this thread).

if ionization radiation baffles you, perhaps consider sunlight? it absolutely can cause cancer - for example if throughout your life you spend one entire august day on the beach under the full sun with most of your skin exposed, two things would happen. immediately, you'd get a incredibly painful sunburn, and over the long term your chances of getting skin cancer would be highly increased. by contrast, if throughout your life, you spend everyday on the beach (assuming you live where the climate allows) exposed to the full sun, you would not be sunburned and your chances of getting skin cancer would be only marginally (if at all) increased. why? well, in this case the answer is fairly obvious, your skin cells produce pigments to give you a tan, and also protect you from solar radiation. in the case of ionizing radiation, the changes in your cells may be less obvious because you can't see them, but they occur just as surely - it's not clear yet what the exact implications for human health are in the case of ionization radiation - but the basic concepts behind hormesis are ancient and have stood the test of time.