CONCEPTS IN BIOLOGY
PART III. MOLECULAR BIOLOGY, CELL DIVISION, AND GENETICS
9. Cell Division—Proliferation and Reproduction
Cancer is a disease caused by the failure to control cell division. This results in cells that divide too often and eventually interfere with normal body function. Scientists view cancer as a disease caused by mutations in the genes that regulate cell division. The mutations can be inherited or caused by agents in the environment. For example, the tar from cigarette smoke has been directly linked to mutations in the p53 gene. The tar in cigarette smoke is categorized as both a mutagen and a carcinogen. Mutagens are agents that mutate, or chemically damage, DNA. Carcinogens are mutagens that cause cancer.
Mutagenic and Carcinogenic Agents
Many agents have been associated with higher rates of cancer. The one thing they all have in common is their ability to alter the sequence of nucleotides in the DNA molecule. When damage occurs to DNA, the replication and transcriptional machinery may no longer be able to read the DNA’s genetic information (figure 9.13). This is a partial list of mutagens that are found in our environment.
FIGURE 9.13. Carcinogens
Carcinogenic agents come in many forms.
X rays and gamma rays
UV-A, from tanning lamps
UV-B, the cause of sunburn
Polyvinyl chloride (PVC)
Chemicals found in smoked meats and fish
Food containing nitrates (e.g., bacon)
Some viruses insert a copy of their genetic material into a cell’s DNA. When this insertion occurs in a gene involved with regulating the cell cycle, it creates an insertion mutation, which may disrupt the cell’s ability to control mitosis. Many of the viruses that are associated with higher rates of cancer are associated with a particular type of cancer (figure 9.14):
Hepatitis B virus (HBV)
Herpes simplex virus (HSV) type II
Human T-cell lymphotropic virus (HTLV-1)
Lymphomas and leukemias
Because cancer is caused by changes in DNA, scientists have found that a person’s genetic makeup may be linked to developing certain cancers. A predisposition to develop cancer can be inherited from one’s parents. The following cancers have been shown to be inherited:
Certain skin cancers
FIGURE 9.14. Cancer Caused by Viruses
Cancer is both environmental and genetic. The hepatitis B virus is among the many agents that can increase the likelihood of developing cancer.
When uncontrolled mitotic division occurs, a group of cells forms a tumor (How Science Works 9.1). A tumor is a mass of cells not normally found in a certain portion of the body. A benign tumor is a cell mass that does not fragment and spread beyond its original area of growth. A benign tumor can become harmful, however, by growing large enough to interfere with normal body functions. Some tumors are malignant. Malignant tumors are harmful because they may spread or invade other parts of the body (figure 9.15). Cells of these tumors metastasize, or move from the original site and begin to grow new tumors in other regions of the body (figure 9.16).
FIGURE 9.15. Skin Cancer
Malignant melanoma is a type of skin cancer. It forms as a result of a mutation in pigmented skin cells. These cells divide repeatedly, giving rise to an abnormal mass of pigmented skin cells. The two large dark areas in the photograph, are the cancer on a person’s back; the surrounding cells have the genetic information to develop into normal, healthy skin. This kind of cancer is particularly dangerous, because the cells break off and spread to other parts of the body (metastasize).
FIGURE 9.16. Metastasizing Cells
A tumor consists of cells that have lost their ability to control cell division. As these cells divide rapidly, they form a tumor and invade surrounding tissues. Cells metastasize when they reach blood vessels and are carried to other parts of the body. Once in their new locations, the cells continue to divide and form new tumors.
HOW SCIENCE WORKS 9.1
The Concepts of Homeostasis and Mitosis Applied
The total number of cells stays about the same during the adult life of an organism. It is kept at a constant number because the number of cells generated by mitosis equals the number that die. This homeostatic condition is achieved when the rate of mitosis equals the rate of cell death:
R(reproduction) = D(death)
Cancer may result if homeostasis is not maintained because cells are reproducing faster than they die:
R > D
For example, pancreatic cancer can result from the malfunctioning of apoptosis-signaling pathways. Signaling pathways are biochemical reactions that trigger events in the cell. In this situation, a form of cancer, pancreatic cells are not signaled to die by apoptosis and they continue to divide unchecked.
On the other hand, if lost cells are not replaced by mitosis, the organism will no longer be able to maintain a stable, constant condition and die:
R < D
Biomedical researchers have applied this knowledge to control cells that have abnormally constant rates of mitosis. For example, certain cancer therapies affect signaling pathways by increasing apoptosis. The drug Taxol causes a significant increase in apoptosis in cancer cells.
Epigenetics and Cancer
Although many cancers are caused by mutations, it is thought that epigenetic effects cause more cancers than mutations. Epigenetics causes changes in the expression of genetic material but does not alter (mutate) the DNA. Cells are constantly manipulating their DNA and histone proteins to regulate gene expression including those controlling cell division. For a variety of reasons, cells may perform these functions improperly. Epigenetic changes important to carcinogenesis are the result of certain chemical reactions that affect the nitrogenous base cytosine and histone proteins. Such chemical changes can lead to malfunctions of oncogenes or tumor-suppressor genes. This allows cells whose division rate had previously been regulated, to begin nonstop division; a critical step in cancer development. These modifications to both DNA and histones are able to be passed on through mitosis and in some cases meiosis.
The Surgical Removal of Cancer
Once cancer has been detected, it is often possible to eliminate the tumor. If the cancer is confined to a few specific locations, it may be possible to remove it surgically. Many cancers of the skin or breast are dealt with in this manner. The early detection of such cancers is important because early detection increases the likelihood that the cancer can be removed before it has metastasized (figure 9.17a). However, in some cases, surgery is impractical. Leukemia is a kind of cancer caused by the uncontrolled growth of white blood cells being formed in the bone marrow. In this situation, the cancerous cells spread throughout the body and cannot be removed surgically. Surgery is also not useful when the tumor is located where it can’t be removed without destroying necessary healthy tissue. For example, removing certain brain cancers can severely damage the brain. In such cases, other treatments may be used, such as chemotherapy and radiation therapy.
Chemotherapy and Radiation Therapy
Scientists believe that chemotherapy and radiation therapy for cancer take advantage of the cell’s ability to monitor cell division at the cell cycle checkpoints. By damaging DNA or preventing its replication, chemotherapy and radiation cause the targeted cancer cells to stop dividing and die. Other chemotherapeutic agents disrupt parts of the cell, such as the spindle, that are critical for cell division. Most common cancers cannot be controlled with chemotherapy alone. Chemotherapy is often used in combination with radiation therapy.
Radiation therapy uses powerful X rays or gamma rays to damage the DNA of the cancer cells (figure 9.17b). At times, radiation can be used when surgery is impractical. This therapy can be applied from outside the body or by implanting radioactive “seeds” into the tumor. In both cases, a primary concern is to protect healthy tissue from the radiation’s harmful effects. When radiation is applied from outside the body, a beam of radiation is focused on the cancerous cells and shields protect as much healthy tissue as possible.
FIGURE 9.17. Surgical and Radiation Treatments of Cancer
(a) Surgery is one option for treating cancer. Sometimes, if the cancer is too advanced or has already spread, other therapies (b) such as radiation are necessary.
Unfortunately, chemotherapy and radiation therapy can also have negative effects on normal cells. Chemotherapy may expose all the body’s cells to the toxic ingredients and then weaken the body’s normal defense mechanisms, because it decreases the body’s ability to reproduce new white blood cells by mitosis. As a precaution against infection, cancer patients undergoing chemotherapy must be given antibiotics. The antibiotics help them defend against dangerous bacteria that might invade their bodies. Other side effects of chemotherapy include intestinal disorders and hair loss, which are caused by damage to the healthy cells in the intestinal tract and the skin that normally divide by mitosis.
Whole-body radiation is used to treat some leukemia patients, who have cancer of the blood-forming cells located in their bone marrow; however, not all of these cells are cancerous. A radiation therapy method prescribed for some patients involves the removal of some of their bone marrow and isolation of the noncancerous cells. The normal cells can then be grown in a laboratory. After these healthy cells have been cultured and increased in number, the patient’s whole body is exposed to high doses of radiation sufficient to kill all the cancerous cells remaining in the bone marrow. Because this treatment can cause significant damage to the immune system, it is potentially deadly. As a precaution the patient is isolated from all harmful substances and infectious microbes. They are fed sterile food, drink sterile water, and breathe sterile air while being closely monitored and treated with antibiotics. The cultured noncancerous cells are injected back into the patient. As if the cells had a memory, they migrate back to their origins in the bone marrow, establish residence, and begin regulated cell division all over again.
Because radiation damages healthy cells, it is used very cautiously. In cases of extreme exposure to radiation, people develop radiation sickness. The symptoms of this disease include hair loss, bloody vomiting and diarrhea, and a reduced white blood cell count. Vomiting, nausea, and diarrhea occur because the radiation kills many of the cells lining the gut and interferes with the replacement of the intestine’s lining, which is constantly being lost as food travels through. Hair loss occurs because radiation prevents cell division at the hair root; these cells must divide for the hair to grow. Radiation reduces white blood cells because it prevents their continuous replacement from cells in the bone marrow and lymph nodes. When radiation strikes these rapidly dividing cells and kills them, the lining of the intestine wears away and bleeds, hair falls out, and there are very few new white blood cells to defend the body against infection.
The use of nanoparticle cancer therapy is being explored in many research labs. Nanoparticles cover a range between 1 and 100 nanometers in diameter and can be synthesized so that they attach only to specific cancer cells taken from a patient. They can be combined with cancer-specific, anticancer proteins. When injected into an organism, these combination particles travel throughout the body without causing harm or being rejected until they attach to their targeted cancer cells. When they combine with cell surface molecules, the anticancer drug is delivered and the cancer cell destroyed. While still in the research phase, nanoparticle cancer therapy has been shown to stop the growth of prostate, breast, and lung tumors in rodents.
9.5. CONCEPT REVIEW
14. Why is radiation used to control cancer?
15. List three factors associated with the development of cancer.
16. What role does epigenetics play in cancer development?