Cancer in Dogs - Mechanism and Cause by
Dr Larry Thornburg, University of Missouri
Cancer in dogs: mechanism and cause....
by Dr. Larry Thornburg, University of Missouri
From normal cell to cancer cell. All organs in your dog are composed of cells. Cells are tiny units that can only be seen with a microscope. Thousands of cells make up each organ in your dog's body. In general, all cells in all organs are alike (in the same manner one can say that all cars are alike). All cells digest food using organelles (literally "tiny organs") called lysosomes. The energy for all cells is supplied by organelles called mitochondria. All cells manufacture proteins using organelles called ribosomes. Each and every cell in your dog's body contains exactly the same DNA (genes, chromosomes). And, the DNA that is in each cell is unique to your dog, different in some ways even from that of his/her littermates.
The nucleus of every cell contains between 60,000 and 100,000 genes. Among those 60,000-plus genes are approximately 100 genes that control cell division. Think about the union of the egg and the sperm giving rise to a single cell. That single cell and the many generations of daughter cells, divide thousands of times over 63 days to produce the normal puppy with bones, muscles, skin, hair, heart, kidneys for example. Over the next several weeks to months those generations of cells composing the
puppy must divide thousands of more times in order for the puppy to grow into the adult dog. The majority of cells never divide again once adult size is reached. Only a few cell types such as bone marrow cells, skin cells and cells of the intestines continue to divide throughout the lifetime of your dog.
More than 50 years of scientific research by thousands of scientists worldwide and billions of dollars have been spent trying to understand cancer. The main question that scientists are trying to answer is, "How do cells know when to divide and when to stop dividing?" "Cancer" is the disease that occurs when the normal control genes in a cell fail and that cell is released to divide relentlessly. Cells of the bone, skin, liver, blood vessels, heart, brain, any cell in your dog's body can become transformed into a
cancer cell.
When cells divide out of control the accumulation of more and more cancerous daughter cells results in crowding out of the normal cells and, eventually, failure of the affected organ. Accumulation of cancerous daughter cells can result in the appearance of an enlarging nodule on the bone or in the skin, for example. In addition, the cancerous daughter cells may have the capacity to reach distant organs (metastasize) by traveling in the blood. Once the mobile cancer cells reach a distant organ,
the relentless cell division also causes failure of that organ (or those organs).
What are "cancer genes"? The nucleus of each cell contains DNA (short for DeoxyriboNucleic Acid). DNA is organized into long structures termed chromosomes. In dogs there are 78 chromosomes. As opposed to your dog, you have 46 chromosomes. Each one of your individual chromosomes is longer that those of your dog. However, you and your dog have approximately the
same total quantity of DNA. Genes are arranged along the chromosomes exactly like beads on a necklace. Those 78 chromosomes of your dog contain 60,000 to 100,000 genes. Those 60,000 to 100,000 genes control every activity that every cell in every organ performs, including cell division.
Some of the 100 genes that control cell division are comparable to the car accelerator and these genes cause cells to divide. However, there is another group of genes that is comparable to the brakes of the car and these genes prevent cells from dividing. Each cell maintains a careful balance of activity between the two groups of control genes. This careful balance allows all cells to divide during development of the puppy. But, that delicate balance changes in the adult dog to prevent the majority of cells from dividing, while allowing controlled division in cells such as blood producing cells. When cell-division-control genes becomes mutated (the DNA changes in chemical structure), the balance is lost forever and uncontrolled cell division (cancer) results. These two groups of genes that control cell division are called "cancer genes." All cancers are the result of mutations in
one or more of the approximately 100 genes that control cell division.
What causes the mutations in the cancer genes? Each day of your dog's life all of the genes of each cell are subjected to a barrage of insults that have the potential to cause a mutation. Toxic chemicals can cause a mutation in DNA. One category of toxic chemicals comes from within the cell. These toxic chemicals are normal products of daily chemical activities within each cell. For the most part, cells have developed mechanisms for detoxifying these waste products. However, some of these toxic waste products escape the protective mechanisms of the cell and attack the cell's DNA.
Another category of toxic chemicals are components of the normal diet. Every diet contains plant matter. All plants have developed various chemical mechanisms to evade being eaten by their natural predators: insects, bacteria, fungus and viruses. The chemicals that are toxic to the natural predators of plants are also toxic to the living cells of your dog in many instances. Some of these naturally occurring chemicals can cause mutations in the DNA. A third category of toxic chemicals is the man-made chemicals. There is a long list of man-made chemicals that are known to cause mutations in the DNA of cells and result in cancer.
Viruses can cause a mutation in a gene. However, there are very few viruses that have been proven to cause cancer in dogs, and at this time it does not appear that viruses are a significant cause of cancer in dogs. Irradiation (the sun's rays) can cause cancer. Cancer caused by irradiation is uncommon in domestic animals except those individuals without pigmentation in their skin. Lifetime exposure to the sun can cause cancer on the white ears or white face of dogs. All of these above are known as
"acquired cancer."
Inherited cancer is somewhat different. All genes are paired (two copies of each gene) within every cell. One copy of the gene comes from the dam and one copy of the gene comes from the sire. With many of the 60,000-plus genes there is not a substantial consequence when one gene of the pair is mutated because the cell has the other (normal) copy to carry on normal function. The two groups of cancer genes (the "accelerator" genes versus the "brake" genes) are somewhat different from each
other. It generally requires only one copy of an "accelerator" gene to be mutated for cancer to occur. However, both copies of a "brake" gene must be mutated for cancer to occur.
When a puppy inherits one mutated copy of a "brake" gene from the dam or the sire, every cell in each organ has only one normal copy to carry out the control of cell division. That puppy has an increased risk of developing cancer relative to dogs with two normal copies of the "brake" gene. If the dog with only one normal copy of the gene suffers a single chemical insult, the affected cell will lose control of cell division and it will become a cancer cell. Dogs do not "inherit" cancer per se. Dogs (and
people) inherit a "susceptibility" to develop cancer. That is, the dog that inherits one abnormal copy of a "brake" gene is more likely to develop cancer in his/her lifetime than is a littermate with two normal copies of the same "brake" gene. Genetic testing attempts to determine if a particular dog inherited (and could consequently pass to the offspring) one abnormal copy of a cancer gene.
Why is treatment of cancer so difficult? Generally, there are three methods by which cancer can be treated. Surgery is a good choice for treatment if the cancer is localized to a single area and the veterinarian has the opportunity to completely remove the cancer. However, some cancers, although localized, occur in areas that are not amenable to surgery (in the wall of the heart for example). Likewise, another cancer may have occurred originally in the skin, but has now spread to several
different areas of the lungs. Surgery would not provide a cure for this dog.
Chemotherapy is a second choice for treatment of cancer. As you can see from the information presented above, cancer is simply a normal process (ie, cell division) that is out of control. Cancer cells are identical to normal cells in every way except the control of cell division (cancer cells have lost the control of cell division). Chemotherapeutic agents are toxic chemicals that are used to kill the cancer cells. However, since all cells in the body are undergoing the exact same living processes, all
chemotherapeutic agents kill normal cells as well as cancer cells. This is the reason why some dogs (and some people) get very sick during the chemotherapy. The drugs and the dose of those drugs that are used for chemotherapy are a delicate balance between killing the cancer cells and killing the normal cells of the body.
Radiation is the third mode of cancer therapy. Radiation has the potential to kill any cell in the body. Again, the idea of radiation therapy for cancer is to localize the destructive beam to the cancer, sparing the normal cells. This can be very successful when the cancer is a solitary nodule and the radiation beam can be focused on the cancer. However, when cancer is widespread (metastatic cancer) it is usually not possible to kill only the cancer cells and radiation is rarely a treatment under such
circumstances.
by Dr. Larry Thornburg, University of Missouri
From normal cell to cancer cell. All organs in your dog are composed of cells. Cells are tiny units that can only be seen with a microscope. Thousands of cells make up each organ in your dog's body. In general, all cells in all organs are alike (in the same manner one can say that all cars are alike). All cells digest food using organelles (literally "tiny organs") called lysosomes. The energy for all cells is supplied by organelles called mitochondria. All cells manufacture proteins using organelles called ribosomes. Each and every cell in your dog's body contains exactly the same DNA (genes, chromosomes). And, the DNA that is in each cell is unique to your dog, different in some ways even from that of his/her littermates.
The nucleus of every cell contains between 60,000 and 100,000 genes. Among those 60,000-plus genes are approximately 100 genes that control cell division. Think about the union of the egg and the sperm giving rise to a single cell. That single cell and the many generations of daughter cells, divide thousands of times over 63 days to produce the normal puppy with bones, muscles, skin, hair, heart, kidneys for example. Over the next several weeks to months those generations of cells composing the
puppy must divide thousands of more times in order for the puppy to grow into the adult dog. The majority of cells never divide again once adult size is reached. Only a few cell types such as bone marrow cells, skin cells and cells of the intestines continue to divide throughout the lifetime of your dog.
More than 50 years of scientific research by thousands of scientists worldwide and billions of dollars have been spent trying to understand cancer. The main question that scientists are trying to answer is, "How do cells know when to divide and when to stop dividing?" "Cancer" is the disease that occurs when the normal control genes in a cell fail and that cell is released to divide relentlessly. Cells of the bone, skin, liver, blood vessels, heart, brain, any cell in your dog's body can become transformed into a
cancer cell.
When cells divide out of control the accumulation of more and more cancerous daughter cells results in crowding out of the normal cells and, eventually, failure of the affected organ. Accumulation of cancerous daughter cells can result in the appearance of an enlarging nodule on the bone or in the skin, for example. In addition, the cancerous daughter cells may have the capacity to reach distant organs (metastasize) by traveling in the blood. Once the mobile cancer cells reach a distant organ,
the relentless cell division also causes failure of that organ (or those organs).
What are "cancer genes"? The nucleus of each cell contains DNA (short for DeoxyriboNucleic Acid). DNA is organized into long structures termed chromosomes. In dogs there are 78 chromosomes. As opposed to your dog, you have 46 chromosomes. Each one of your individual chromosomes is longer that those of your dog. However, you and your dog have approximately the
same total quantity of DNA. Genes are arranged along the chromosomes exactly like beads on a necklace. Those 78 chromosomes of your dog contain 60,000 to 100,000 genes. Those 60,000 to 100,000 genes control every activity that every cell in every organ performs, including cell division.
Some of the 100 genes that control cell division are comparable to the car accelerator and these genes cause cells to divide. However, there is another group of genes that is comparable to the brakes of the car and these genes prevent cells from dividing. Each cell maintains a careful balance of activity between the two groups of control genes. This careful balance allows all cells to divide during development of the puppy. But, that delicate balance changes in the adult dog to prevent the majority of cells from dividing, while allowing controlled division in cells such as blood producing cells. When cell-division-control genes becomes mutated (the DNA changes in chemical structure), the balance is lost forever and uncontrolled cell division (cancer) results. These two groups of genes that control cell division are called "cancer genes." All cancers are the result of mutations in
one or more of the approximately 100 genes that control cell division.
What causes the mutations in the cancer genes? Each day of your dog's life all of the genes of each cell are subjected to a barrage of insults that have the potential to cause a mutation. Toxic chemicals can cause a mutation in DNA. One category of toxic chemicals comes from within the cell. These toxic chemicals are normal products of daily chemical activities within each cell. For the most part, cells have developed mechanisms for detoxifying these waste products. However, some of these toxic waste products escape the protective mechanisms of the cell and attack the cell's DNA.
Another category of toxic chemicals are components of the normal diet. Every diet contains plant matter. All plants have developed various chemical mechanisms to evade being eaten by their natural predators: insects, bacteria, fungus and viruses. The chemicals that are toxic to the natural predators of plants are also toxic to the living cells of your dog in many instances. Some of these naturally occurring chemicals can cause mutations in the DNA. A third category of toxic chemicals is the man-made chemicals. There is a long list of man-made chemicals that are known to cause mutations in the DNA of cells and result in cancer.
Viruses can cause a mutation in a gene. However, there are very few viruses that have been proven to cause cancer in dogs, and at this time it does not appear that viruses are a significant cause of cancer in dogs. Irradiation (the sun's rays) can cause cancer. Cancer caused by irradiation is uncommon in domestic animals except those individuals without pigmentation in their skin. Lifetime exposure to the sun can cause cancer on the white ears or white face of dogs. All of these above are known as
"acquired cancer."
Inherited cancer is somewhat different. All genes are paired (two copies of each gene) within every cell. One copy of the gene comes from the dam and one copy of the gene comes from the sire. With many of the 60,000-plus genes there is not a substantial consequence when one gene of the pair is mutated because the cell has the other (normal) copy to carry on normal function. The two groups of cancer genes (the "accelerator" genes versus the "brake" genes) are somewhat different from each
other. It generally requires only one copy of an "accelerator" gene to be mutated for cancer to occur. However, both copies of a "brake" gene must be mutated for cancer to occur.
When a puppy inherits one mutated copy of a "brake" gene from the dam or the sire, every cell in each organ has only one normal copy to carry out the control of cell division. That puppy has an increased risk of developing cancer relative to dogs with two normal copies of the "brake" gene. If the dog with only one normal copy of the gene suffers a single chemical insult, the affected cell will lose control of cell division and it will become a cancer cell. Dogs do not "inherit" cancer per se. Dogs (and
people) inherit a "susceptibility" to develop cancer. That is, the dog that inherits one abnormal copy of a "brake" gene is more likely to develop cancer in his/her lifetime than is a littermate with two normal copies of the same "brake" gene. Genetic testing attempts to determine if a particular dog inherited (and could consequently pass to the offspring) one abnormal copy of a cancer gene.
Why is treatment of cancer so difficult? Generally, there are three methods by which cancer can be treated. Surgery is a good choice for treatment if the cancer is localized to a single area and the veterinarian has the opportunity to completely remove the cancer. However, some cancers, although localized, occur in areas that are not amenable to surgery (in the wall of the heart for example). Likewise, another cancer may have occurred originally in the skin, but has now spread to several
different areas of the lungs. Surgery would not provide a cure for this dog.
Chemotherapy is a second choice for treatment of cancer. As you can see from the information presented above, cancer is simply a normal process (ie, cell division) that is out of control. Cancer cells are identical to normal cells in every way except the control of cell division (cancer cells have lost the control of cell division). Chemotherapeutic agents are toxic chemicals that are used to kill the cancer cells. However, since all cells in the body are undergoing the exact same living processes, all
chemotherapeutic agents kill normal cells as well as cancer cells. This is the reason why some dogs (and some people) get very sick during the chemotherapy. The drugs and the dose of those drugs that are used for chemotherapy are a delicate balance between killing the cancer cells and killing the normal cells of the body.
Radiation is the third mode of cancer therapy. Radiation has the potential to kill any cell in the body. Again, the idea of radiation therapy for cancer is to localize the destructive beam to the cancer, sparing the normal cells. This can be very successful when the cancer is a solitary nodule and the radiation beam can be focused on the cancer. However, when cancer is widespread (metastatic cancer) it is usually not possible to kill only the cancer cells and radiation is rarely a treatment under such
circumstances.