[ RadSafe ] A scientific explanation of hormesis

[Scott, Bobby]

Dear Tariq:

 

Related to your comment in Radsafe Digest Volume 9, Issue 3 on 14 Sept.
2005.

 

Regarding the role of hydrogen peroxide in protecting us from cancer
(hormetic effect), we have described a protective apoptosis-mediated
(PAM) process that is activated by low-dose, low-LET radiation (e.g. X
and gamma rays) that selectively removes mutants and precancerous cells,
thereby protecting from cancer occurrence (and from other diseases).
The PAM process involves hydrogen peroxide (and other chemical species
and cytokines). Our poster given last week at the 9th International
Conference on Environmental Mutagens in San Francisco described our most
recent research results related to the PAM process.  The poster is
entitled "Basic research results that do not support the BEIR VII report
conclusions regarding the linear-no-threshold risk hypothesis" and a pdf
version is available via our website: http://www.radiation-scott.org
<http://www.radiation-scott.org/> .  Just go to the "Low Dose Research"
section of the webpage and click on the poster.

 

The NEOTRANS3 model described in the poster can lead to hormetic-type
dose-response curves for induced mutations and induced neoplastic
transformation (early step in cancer induction).  The hormetic
dose-response curve arises in part from low dose induced PAM (presumed
to not depend on the p53 tumor suppressor gene) and low dose induced
high efficiency DNA repair/apoptosis (presumed to not depend on p53).
The p53-dependent component suppresses the formation of new mutants and
transformed cells.  The p53-independent PAM process removes already
existing mutants and transformed cells as well as newly formed mutants
and transformed cells. High doses however inhibit the PAM process.  This
leads to hormetic-type dose-response curves for mutation induction and
for inducing neoplastic transformation in cell culture studies.  The
indicated protective processes along with stimulation of the immune
system are considered to jointly protect against cancer induction in
humans and in animals.  However, high doses also inhibit immune system
functioning.  Thus, hormetic-type dose response curves are also expected
and have been observed for cancer induction by low-LET radiation.

 

The indicated protective processes however are transient, considered to
last only for relatively short times.  However, our modeling research
indicates that for protracted exposure to low-LET radiation, the
protective processes can be over and over reactivated.  This is expected
to have two important impacts: (1) to provide enhanced protection from
cancer; (2) greatly extend the dose zone over which the protection is
activated.  Thus, for brief exposures at high rates to gamma rays, as
occurred in Hiroshima and Nagasaki, little protection and only at very
low doses would be expected.  However, for persons living in regions of
the world with high background low-LET radiation, much greater
protection and over a much broader dose range would be expected.  The
indicated extended protection would also be expected for nuclear workers
(e.g. at DOE facilities in the US who received low level protracted
exposure), for airline pilots and flight attendance receiving chronic
low-level irradiation, and for resident of the apartments in Taiwan that
were built of cobalt-60 contaminated steal.

 

For a population receiving chronic radiation exposure at very low rates
(in excess of average background) from man-made sources,  our modeling
research leads to the following dose-response function for the relative
risk (RR) for cancer induction (applicable to low doses and dose rates):

 

RR = 1 - PROFAC, for doses (from man-made sources) > 0.

RR = 1, otherwise.

 

The protection factor (PROFAC) gives the proportion of the populations
that will have cancer prevented as a result of their radiation exposure
(and is expected to depend on dose rate and length of exposure).  For
example, in a population for which 100,000 cancer deaths would be
expected in the absence of exposure to radiation from the man-made
source, a PROFAC=0.25 would mean that 25,000 deaths from cancer would
have been prevented as a result of their chronic radiation exposure.
Note that there is no dose term present in the above equation.  This
means that arguments used by some to exclude ecological data form their
low-dose risk assessment (e.g. BEIR VII) based on dose errors being too
large may be irrelevant (since dose may not be needed for a risk
assessment [i.e., population risk-reduction assessment]).

 

On yesterday, I gave a presentation at the ANS sponsored PSA '2005
Meeting in San Francisco.  The LNT Plenary Session presentation was
entitled "The LNT hypothesis may have outlived its usefulness for
low-LET radiation". The session was chaired by Dr. Chauncey Starr. In my
presentation I gave PROFAC estimates for various populations of humans
exposed to low-LET radiations.  Most were based on a paper by Z.
Jaworowski  ("Ionizing radiation in the 20th century and beyond."
Symposium "Entwicklungen im Strahleschutz". Munich, 29 November 2001).
Some presented results are summarized below and should be enlightening:

 

Population [US, high background area], effect [cancers], PROFAC = 0.15
(relative to average)

 

Population [Canadian nuclear industry workers], effect [leukemia],
PROFAC = 0.68

 

Population [US DOE labs workers], effect [leukemia], PROFAC = 0.78

 

Population [Taiwanese in Co-60 contaminated (steel) apartments], effect
[cancers], PROFAC > 0.95

 

Please note that these are profound effects!  Not like the minuscule
theoretical increases in risk calculated using LNT extrapolated from
high dose and high dose rate data such as for A-bomb survivors (as were
used in BEIR VII along with DDREF). 

 

LNT does not appear to apply to chronic exposure at very low rates
(low-dose exposure) to populations comprised of all ages or to adult
populations.  The RR equation (developed based on our NEOTRANS3 model)
presented above appears to be more appropriate. Risk will eventually
increase (leading RR > 1) if dose is high enough (dose term then is
needed).  This curve shape is hormetic.  LNT is expected to eventually
emerge but only after high doses for the indicated populations.

 

Best wishes,

Bobby R. Scott

LRRI, Albuquerque, NM USA