Cancer And Phytochemicals
by Susan Thorpe-Vargas
Ph.D
Cancer Is
Epidemic In Dogs and Pandemic In Cats
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.
http://www.thedogplace.org/HEALTH/cancer-epidemic-elligac-acid.asp
#0611.1112
related articles:
Why Dogs
Get Cancer
Dr. Susan Thorpe-Vargas Docvite@aol.com has a Ph.D. in Immunology and wrote for DOG World
magazine for almost 20 years. She is a multiple Maxwell Award nominee and has
won twice. In addition, she has won the Eukanuba Health Award two times. Her
work has been translated into many different languages. She has bred and shown
Samoyed for 22 years and shares her home with two Sammies, Max and Chloe and
Sidney-the rescue Siamese.