Whatever doesn't kill you might make you stronger
By Rebecca Renner
Image: RALPH WHITE Corbis
POLLUTION STANDARDS that factories--such as
this chemical plant on Lake Baikal, Russia--must meet may change if hormesis
proves to be a widespread phenomenon.
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.
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.
may sound bizarre, but such adaptation to stress is common, says physiologist
Suresh Rattan of Århus University in Denmark. Exercise, for instance, plays
biochemical havoc with the body: starving some cells of oxygen and glucose,
flooding others with oxidants, and depressing immune functions. "At first
glance, there is nothing good for the body about exercise," he notes. But
even couch potatoes know that moderate exercise is worthwhile. Rattan says that
the cellular insults from exercise prompt the defense system to work more
Over the past
decade, Calabrese has compiled thousands of examples of hormesis from published
scientific literature. Many findings challenge and even flout established
theories about what is harmful. For example, the prevailing theory is that any
increase in radiation exposure increases the risk of cancer. But biologist
Ronald Mitchel of Atomic Energy of Canada has shown that a single low dose of
ionizing radiation stimulates DNA repair, delaying the onset of cancer in mice;
high doses produced the opposite effect, as expected. Prolonged exposure to
extreme temperatures is also harmful, but Rattan has found that heating up
human skin cells to 41 degrees Celsius (106 degrees Fahrenheit) twice a week
for an hour slows aging in the cells.
well-established environmental headaches display some hormesis. The definitive
rat study that linked high doses of dioxin to cancer, published in 1978 by
Richard Kociba of Dow Chemical and his colleagues, also found that low doses
reduced the incidence of tumors.
Image: LUCY READING; ADAPTED FROM
J. R. MAISIN ET AL. IN RADIATION RESEARCH, FEBRUARY 1988 (top)
AND TETSUYA ABE ET AL. IN BIOCHEMICAL PHARMACOLOGY, JULY 1, 1999 (bottom),
AS REPRODUCED BY EDWARD J. CALABRESE AND LINDA A. BALDWIN IN TRENDS IN
PHARMACOLOGICAL SCIENCES, JUNE 2001
A PINCH OF POISON seems beneficial in
some cases when compared with control groups, as shown by the effects of
gamma rays on the emergence of mouse tumors (top) and of cadmium
exposure on human ovarian cells (bottom).
to such stresses is absolutely essential," Mitchel remarks. "If we
couldn't adapt to changes in our environment, we would die." Such
adaptation at the molecular level is seen in most primitive forms of life and
has been evolutionarily conserved all the way up to humans, he adds.
challenges the existing hazard-assessment process underlying environmental
regulations, Calabrese says. Toxicologists usually determine the relation
between exposure to contaminants and health risks by conducting animal
experiments. They start out by giving lab animals a high dose that produces
clear adverse effects. Then they work downward until they can estimate a
concentration that doesn't cause harmful effects. For chemicals that don't
cause cancer, they obtain a safe dose for humans by applying uncertainty
factors to account for differences between mice and men and among individual
people. The resulting safe dose for humans is then usually deemed to be about
0.01 to 0.001 the safe dose for mice. For carcinogens, toxicologists assume
that exposure to any amount increases the risk.
suspects that in many cases, the benefits of hormesis may occur at levels
higher than the recommended safe doses for humans. Thus, it might be possible
to refine pollution standards so that we can reap the benefits of hormesis
while still being protected against adverse effects in the environment. Or at
the very least, it might be reasonable to stop worrying about exceedingly low
investigating adaptive stress responses aren't the only ones interested in
effects at low doses. Scientists studying endocrine disruption are also joining
in. They are concerned that contaminants that mimic hormones can have
significant harmful effects at very low doses if exposure occurs during a
susceptible developmental window. In some sense, endocrine disruption appears
to be the opposite of hormesis, in which low doses could have unsuspected
harmful effects because of the contaminant's chemical similarity to hormones.
molecular biology are giving toxicologists the tools to investigate low-dose
phenomena, according to Joseph V. Rodricks, health sciences director at
Environ, environmental consultants in Arlington, Va. Instead of monitoring the
onset of disease or cancer, toxicologists are beginning to use modern molecular
biology tools to identify the critical early precursors to illness. They then
monitor how the precursors vary at low doses.
much to prove if it is to revolutionize toxicology, Rodricks notes. Many of the
hormetic dose-response relations that Calabrese has compiled raise more
questions than answers, he says. For example, the dioxin study looks like
hormesis if all types of cancer are combined, but hormesis doesn't show for individual
types of cancer. Despite such skepticism, Rodricks is one of many toxicologists
calling for a National Research Council review of this phenomenon.