Cancer And Phytochemicals
by Susan Thorpe-Vargas Ph.D
It seems that our pets are particularly at risk for cancer because they interact
so closely with the environment (unless of course you lick your paws after
crossing the street). Other outside influences can also be responsible for the
mutations and changes in cellular genetics that lead to cancer. Because we all
breathe an atmosphere that contains oxygen, our bodies are constantly producing
free radicals--highly reactive oxygen molecules that occur naturally in the body
because of metabolic processes. Environmental factors such as air pollution,
radiation, pesticides, herbicides, many drugs and exposure to cigarette smoke
react within the body to cause free radical production. Dogs with squashed up
noses, like pugs and certain breeds of cats, are especially vulnerable to
second-hand cigarette smoke. Free radicals can damage DNA, affect the structure
and function of cell membranes and damage certain regions of proteins that have
enzymatic functions. Older animals are more at risk due in part to increased
levels of free radicals as well as an impaired ability of their immune systems
to eliminate altered cells. Very inbred dogs also have weakened immune function.
http://cc.ysu.edu/~helorime/inbrimmune.html
Inbreeding Leads To Loss Of Immune Function
In order to function, the immune system has to be able to recognize “self” from
“non-self”. The portion of the genome that codes for the genes that help us
recognize “self” is called the MHC--the Major Histocompatability Complex. These
genes are located very close to each other and therefore it is very rare for
recombination to occur. This in effect means that the genes from each parent are
inherited intact as haplotypes.
If the parents are closely related, then the possibility exists that they share
the same genes at that site, i.e., they are homozygous by decent. In a highly
inbred population, what is the likelihood that the parents share the same
haplotypes? What happens to the puppies or kittens that inherit a duplicate copy
of that same haplotypes? This would essentially cut the functionality of the
immune response in half - not a good thing.
Spay-Neuter Can Affect Susceptibility To Cancer
Altering dogs can affect their susceptibility to cancer. In females, spaying
before their first heat cycle reduces the risk of mammary tumors to 0.05%. It
increases to 8% after one heat cycle and goes up to 26% after the second heat.
Obviously, there must be hormonal factors contributing to this trend.
On the other hand, early spay and neuter actually increases the probability that
cancer will occur in certain canine populations. One study showed that spayed
females were 5 times more likely to develop hemangiosarcoma and neutered males
had a 2.4 times greater risk then intact dog to develop this type of cancer.
Another study, involving 3218 dogs, showed that males, neutered before one year,
had a significant increase in the incidence of bone cancer. A similar study
showed that this risk was twice as high for neutered dogs as it was for intact
males. Although it is commonly believed that altering dogs will improve their
risk of cancer current studies do not support this idea. The only exception is
neutered dogs will never develop testicular cancer.
Cancer Is The # 1 Disease-Related Death In Dogs
It is believed that about 65 million pet dogs are at risk of developing cancer
just in the United States and twenty-three percent of all dogs, regardless of
age, and 45 percent of dogs ten years of age or older die of cancer. Man's best
friend has a cancer rate comparable to humans, and shares many of the basic
biological features. We differ only in the types of cancer we tend to develop.
Cats are more likely to develop lymphomas, especially those who are infected
with Feline Leukemia virus, and injections site sarcomas. Not surprisingly, cats
infected with Feline Immunodeficiency virus are more susceptible to all types of
cancers. The age of onset 15 years ago used to be between 2-5 years of age, but
now it is most likely to be seen between 8-10 and occur somewhere in the GI
tract. Although not as common as cats, dogs are also more frequently diagnosed
with lymphomas and sarcomas, whereas humans primarily develop breast, prostate
and lung cancers. Whatever their name, these cancers are always caused by a
breakdown in the biological control over cellular growth that we now know
results from alterations in the genes that mediate normal cell replication and
cellular death.
Cancer: The Disease With A Thousand Faces
Cancer is not just one disease but is the general name for more than 200
different types of malignancies. Cancers are classified by the tissue type from
which they arise. To illustrate:
? osteosarcoma-bone cancer
? melanoma-skin cancer
? lymphoma-cancer of lymph nodes
? leukemia – blood cancer
Every cellular type has its own form of cancer. The one thing all cancers share
in common is uncontrolled growth. Cancer occurs when cells lose control over
critical checkpoints during the process of one cell splitting and becoming two
cells. This control over cellular replication is in the hands of several
specific types of genes.
Two classes of genes are suspected of being associated with the occurrence of
cancer. A mutation in a tumor suppressor gene is like having faulty brakes in
your car. Just as their name implies, tumor suppressor genes function by making
sure there are no mistakes in the genes that are replicated prior to one cell
becoming two. In this "quality control" process, if errors are detected, the
cell is instructed not to divide. Thus, tumor suppressor genes put the brakes on
cellular division. The other class of genes thought to be involved with
preventing cancer is called proto-oncogenes. Researchers have found that these
genes "code" for proteins involved in mechanisms that regulate the social
behavior of cells. Signals from those cells in the immediate environment induce
their neighbors to divide, differentiate and even undergo apoptosis. So, this
type of gene is involved in promoting the normal growth and division of cells
and could be likened to your car's accelerator. A change in the genetic message
- a mutation, can turn the proto-oncogene into an oncogene and cause your
accelerator to become stuck, thus initiating "runaway" cellular replication.
Nevertheless, there seem to be no pattern to these mutations. What is so
frustrating for both researchers and clinicians alike is that different
combinations of mutations are found in different types of cancer and even in
cancers of supposedly the same type in different patients. What is most
important to remember is that cancer begins as a single abnormal cell that
somehow is able to hide from the body’s defense system and begins to multiply
out of control.
One Natural Cancer Fighter Is Ellagitannins
Multiple studies have discovered that phytonutrients found in raspberries are
able to protect us from cancer and can even shrink some types of cancer tumors.
These substances can also act as an antibacterial and as an antiviral agent. The
highest levels are found in raspberries, but the ellagitannins are also in
certain types of grapes, strawberries, blackberries, blueberries and some nuts
too. In 2001, a study published by Dr. Gary Stoner at Ohio State University,
showed that components in the seeds and berry, but particularly ellagitannins,
inhibited the initiation and promotion/progression stages of esophageal cancer
in a dog. Considering the potential benefits, this is an extremely important
finding. In addition, edible berries, including raspberries also inhibit
angiogenesis. This is a term used to describe the development of blood vessels
needed for tumor growth.
We do not as yet know all of the functions of the ellagitannins in terms of
cancer. A study at Hollings Cancer Center, Medical University of South Carolina
has shown one of the ways they work is to "turn on" a normal cellular process
called apoptosis. Apoptosis is "science speak" for something called programmed
cell death. This natural cell death is just one of several ways the body
protects itself from cancer. In aging animals, cellular replication mistakes can
occur. Cancer cells somehow become immune to the signals that cause cells to
self-destruct, so they become virtually immortal and reproduce indefinitely.
What Causes Cancer Mutations?
We and our pets live in a polluted environment. For instance, the outgassing
from asphalt on a hot summer day produces the deadly carcinogen benzo{a}pyrene,
the same chemical found on meat that has been charcoal broiled. This is just but
one example. Exposure to pesticides and other such chemicals in the environment
can cause the mutations in genetic material that lead to cancer. Even normal
metabolic processes like breathing and exercise produce free radicals that can
wreak havoc on our cellular DNA. We can protect our animals from mutations
caused by environmental toxins and free radicals by giving them antioxidants.
Guess what? Ellagitannins are also very good antioxidants and chemoprotective
agents. Researchers at Wayne State University have a theory about how
ellagitannins might work. The liver produces enzymes that rid the body of
toxins. These enzymes break down or chemically change toxic substances we ingest
or inhale so that they can be excreted. During this detox process, the breakdown
products, called metabolites, are frequently more damaging then the original
substance. It appears that ellagitannins are able to safeguard the liver from
damage caused by these breakdown products. Another theory held by some
investigators is that ellagitannins are able to protect our genetic material
from certain types of chemical reactions that lead to misreading of damaged DNA.
It is becoming clear that normal therapeutic cancer treatment works by turning
on apoptosis. We used to think that chemotherapy and radiation killed rapidly
dividing cells, which is why these procedures were able to shrink tumors.
However, at some point these treatments begin to lose their effectiveness. Why
is that? Scott Lowe, a research scientist at Cold Spring Harbor Laboratory may
have found the answer. Instead of killing these cells, chemotherapy and
radiation damage their cellular DNA. This alerts the cellular watchdogs that
control the cell cycle that something is wrong and tells the cell to stop
dividing or to commit suicide. Therefore, chemotherapy and radiation act
somewhat like a "vaccination" that works by helping the body help itself. The
evidence for Dr. Lowe's theory is pretty convincing, because when these
treatments start to fail, researchers have found that the genes that control
apoptosis are no longer functioning.
As we know, cancer cells become immortal; this means that they are able to
replicate themselves after something called the Hayflick limit has been reached.
The Hayflick limit is the number of "allowed" cellular replications. Each cell
type has its own limit. Human cancer studies show that mutations in the tumor
suppressor gene called p53 account for many of the tumors found. One of the
functions of this gene is that it normally prevents cells with damaged DNA from
proceeding through the cell cycle. The presence of the protein product encoded
by p53 turns on the waf-1 gene. The waf-1 gene produces a protein that normally
inhibits the activity of several similar cellular proteins called kinases. These
proteins are involved in stopping cell cycle progression. A mutation in either
the p53 or waf-1 gene can cause the loss of that "emergency brake" function and
allow uncontrolled growth. However, only "damaged" cells are induced to commit
suicide and so normal cells are not affected.
Other Phytochemicals Found In Raspberries
Besides ellagitannins, the short list of other beneficial compounds found in red
raspberries includes anthocyanins, salicylic acid, quercitin and catechins. Some
recent work has shown that these anthocyanins are more effective then Vitamin E
and equivalent to ibuprofen and naproxen in inhibiting the COX-1 and COX-2
enzymes. Both Cox-1 and Cox-2 are associated with the pain of arthritis and
other inflammatory diseases, and Cox-2 inhibition is positively linked to
preventing breast cancer. Funding for this specific research in dogs has been
supported by the AKC Health Foundation and several breed clubs.
Other than their anticancer properties, anthocyanins provide many other health
benefits. Among these are controlling diabetes, improving circulation and aiding
the retention of motor skills and preventing the loss of memory due to aging.
Dogs do become senile. In canines it is called canine cognitive dysfunction, aka
as “doggie Alzheimer’s” Salicylic acid may have the same effects as aspirin in
protecting us from cancer and the progression of atherosclerosis. Both quercitin
and catechins are flavonals that are known to have antioxidant benefits
including cancer prevention, and quercitin may act as an antihistamine also.
Besides the anticancer properties of ellagitannins they can protect us against
infections.
Ellagitannins can act as antibacterial agents and as antiviral agents too, and
now we know how. Think of the genetic material of bacteria as a rubber band that
is all twisted up. In order to replicate, the DNA must untwist itself through a
process requiring the enzyme gyrase. Ellagitannins inhibits gyrase activity so
replication of the bacterial DNA is restricted. More importantly, bacteria
cannot easily become resistant to this type of antibacterial action. Resistance
to antibiotics has become a real concern to the international medical and
veterinary community. A federal government task force noted that antibiotic
resistance was “a growing menace to everyone” but both young and old animals,
and those with weakened immune systems are especially at risk. Besides its
antibacterial action, ellagitannins have antiviral activity also. Viruses do not
have the ability to replicate themselves. Instead they must "hijack" the host
cell and insert their own DNA into the host cell genome. This requires several
enzymes and ellagitannins inhibit these enzymes also. It especially helpful with
the retroviruses, like FIV (Feline Immunodeficiency virus) as well as feline
leukemia virus (FeLV), as it specifically inhibits reverse transcriptase.
The Protective Effects Of Ellagic Acid
Our companion animals also suffer from diabetes, especially cats, and in dogs
the Samoyed breed is extremely susceptible. Diabetes m. is wide-spread in cats
because they are eating a grain based diet and, as obligate carnivores, they
should be eating meat instead. The disease is common in the Samoyed because they
are genetically predisposed to Type I Diabetes mellitus. New data shows that
ellagic acid is very effective in preventing damage to the eyes, kidneys, heart
and the small capillaries of the feet that occur with high glucose levels. It
does this by inhibiting an enzyme called aldose reductase. This enzyme is
responsible for the production of protein-sugar products called AGE (Avanced
Glycation End-Products). These end products cause the damage of small blood
vessels that leads to the blindness, kidney damage, stroke and heart attacks and
loss of limbs associated with both forms of diabetes. In addition, ellagic acid,
as well as several other constituents in raspberry seed powder, enhance insulin
action, decrease insulin resistance and lower blood sugar, and have multiple
anti-inflammatory effects and decrease oxidative stress as well as lower blood
pressure.
Just like in human medicine many people are turning to alternative forms of
veterinary treatment and prevention. We also share a similar biology and live in
the same environment, so research and treatment for many chronic illnesses, as
well as cancer, can benefit our companion animals as well as ourselves. Thus,
the positive effect of raspberry ellagitannins upon their life expectancy and
the enumerable protective effects of ellagic acid correlate directly to the
health of our beloved pets.
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