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Chapter: Medical Physiology: Introduction to Physiology: Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction

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Cancer

Cancer is caused in all or almost all instances by muta-tion or by some other abnormal activation of cellulargenes that control cell growth and cell mitosis. The abnormal genes are called oncogenes.

Cancer

Cancer is caused in all or almost all instances by muta-tion or by some other abnormal activation of cellulargenes that control cell growth and cell mitosis. The abnormal genes are called oncogenes. As many as 100 different oncogenes have been discovered.

Also present in all cells are antioncogenes, which suppress the activation of specific oncogenes. There-fore, loss of or inactivation of antioncogenes can allow activation of oncogenes that lead to cancer.

Only a minute fraction of the cells that mutate in the body ever lead to cancer. There are several reasons for this. First, most mutated cells have less survival capa-bility than normal cells and simply die. Second, only a few of the mutated cells that do survive become cancerous, because even most mutated cells still have normal feedback controls that prevent excessive growth.

Third, those cells that are potentially cancerous are often, if not usually, destroyed by the body’s immune system before they grow into a cancer. This occurs in the following way: Most mutated cells form abnormal proteins within their cell bodies because of their altered genes, and these proteins activate the body’s immune system, causing it to form antibodies or sen-sitized lymphocytes that react against the cancerous cells, destroying them. In support of this is the fact that in people whose immune systems have been sup-pressed, such as in those taking immunosuppressant drugs after kidney or heart transplantation, the prob-ability of a cancer’s developing is multiplied as much as fivefold.

Fourth, usually several different activated onco-genes are required simultaneously to cause a cancer. For instance, one such gene might promote rapid reproduction of a cell line, but no cancer occurs because there is not a simultaneous mutant gene to form the needed blood vessels.

But what is it that causes the altered genes? Con-sidering that many trillions of new cells are formed each year in humans, a better question might be, Why is it that all of us do not develop millions or billions of mutant cancerous cells? The answer is the incredible precision with which DNA chromosomal strands are replicated in each cell before mitosis can take place, and also the proofreading process that cuts and repairs any abnormal DNA strand before the mitotic process is allowed to proceed. Yet, despite all these inherited cellular precautions, probably one newly formed cell in every few million still has significant mutant characteristics.

Thus, chance alone is all that is required for muta-tions to take place, so we can suppose that a large number of cancers are merely the result of an unlucky occurrence.

However, the probability of mutations can be increased manyfold when a person is exposed to certain chemical, physical, or biological factors, includ-ing the following:


1. It is well known that ionizing radiation, such as x-rays, gamma rays, and particle radiation from radioactive substances, and even ultraviolet light can predispose individuals to cancer. Ions formed in tissue cells under the influence of such radiation are highly reactive and can rupture DNA strands, thus causing many mutations.


2. Chemical substances of certain types also have ahigh propensity for causing mutations. It was discovered long ago that various aniline dye derivatives are likely to cause cancer, so that workers in chemical plants producing such substances, if unprotected, have a special predisposition to cancer. Chemical substances that can cause mutation are called carcinogens. The carcinogens that currently cause the greatest number of deaths are those in cigarette smoke. They cause about one quarter of all cancer deaths.

 

3. Physical irritants also can lead to cancer, such ascontinued abrasion of the linings of the intestinal tract by some types of food. The damage to the tissues leads to rapid mitotic replacement of the cells. The more rapid the mitosis, the greater the chance for mutation.

 

4. In many families, there is a strong hereditarytendency to cancer. This results from the fact thatmost cancers require not one mutation but two or more mutations before cancer occurs. In those families that are particularly predisposed to cancer, it is presumed that one or more cancerous genes are already mutated in the inherited genome. Therefore, far fewer additional mutations must take place in such family members before a cancer begins to grow.

 

5. In laboratory animals, certain types of viruses can cause some kinds of cancer, including leukemia. This usually results in one of two ways. In the case of DNA viruses, the DNA strand of the virus can insert itself directly into one of the chromosomes and thereby cause a mutation that leads to cancer. In the case of RNA viruses, some of these carry with them an enzyme called reversetranscriptase that causes DNA to be transcribedfrom the RNA. The transcribed DNA then inserts itself into the animal cell genome, leading to cancer.


Invasive Characteristic of the Cancer Cell. The major dif-ferences between the cancer cell and the normal cell are the following: (1) The cancer cell does not respect usual cellular growth limits; the reason for this is that these cells presumably do not require all the same growth factors that are necessary to cause growth of normal cells. (2) Cancer cells often are far less adhe-sive to one another than are normal cells. Therefore, they have a tendency to wander through the tissues, to enter the blood stream, and to be transported all through the body, where they form nidi for numerous new cancerous growths. (3) Some cancers also produce angiogenic factors that cause many new blood vesselsto grow into the cancer, thus supplying the nutrients required for cancer growth.

Why Do Cancer Cells Kill? The answer to this questionusually is simple. Cancer tissue competes with normal tissues for nutrients. Because cancer cells continue to proliferate indefinitely, their number multiplying day by day, cancer cells soon demand essentially all the nutrition available to the body or to an essential part of the body. As a result, normal tissues gradually suffer nutritive death.


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