You might be interested in reading an excerpt from Dimensions

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1 Take notes (minimum 1 page) on the following reading. Then review using the animation (link at bottom) and answer the quiz questions at the bottom of the webpage. To get credit for this assignment you must turn in notes, get all 5 quiz questions right, and me the quiz results. Cell Division and Cancer You might be interested in reading an excerpt from Dimensions of Cancer, by Charles E. Kupchella. Perhaps you already know that you have one chance in three of getting cancer; one chance in five of dying of it. Perhaps you have, or have had, friends or family members with cancer. Each year, cancer kills almost a half-million Americans; it is second only to heart disease as a cause of death in the United States. Later, I will give you some statistics about cancer in the United States. In its most fundamental sense, cancer is a family of diseases, primarily of the old and the very young, in which cells divide, move around the body, and secrete things as if the rest of the organism had no control over them. Let's look at how cells reproduce. The process is known as cell division where the cellular contents are divided between two new daughter cells.

2 An individual grows by taking in raw materials from the environment and uses these raw materials to synthesize new structural and functional molecules. When the cell reaches a certain critical size and metabolic state, it divides. The new cells are structurally and functionally similar to each other. I say similar because the two daughter cells receive about half rather than exactly half of their parent's cytosol and organelles. Much more important, however, is that each daughter cells inherits an exact replica of the heredity information or genome of the parent cell. In prokaryotes, distributing exact replicas of hereditary information is relatively simple. Prokaryotes have their hereditary material present as a single, long, circular strand of DNA with their associated proteins. This molecule, the prokaryote's chromosome, is replicated just prior to division. Each of the two daughter chromosomes attaches to the parent plasma membrane and as the membrane elongates, the chromosomes move apart. After the chromosomes are well separated, the cell pinches apart to become two new cells. In eukaryotes, the problem of distributing the hereditary material equally is much more complex. A typical eukaryote cell contains perhaps 1,000 times as much DNA as a prokaryote cell and this DNA is linear, forming a number of distinct chromosomes. Humans, for instance, have 46 chromosomes. When human cells divide, each daughter cell has to receive one copy-- and only one copy--of each chromosome. The solution is elaborate. In a series of steps called mitosis, each daughter cell is provided with complete set of chromosomes. Mitosis is usually followed by cytokinesis or cytoplasmic

3 division, a process that divides the parent cell into two daughter cells. Dividing eukaryote cells pass through a regular, repeated sequence of cell growth and division known as the cell cycle. The cycle consists of five major phases: G1 S G2 mitosis cytokinesis You might wish to examine a diagram of what goes on during these five major phases. Completion of the cycle takes from a few hours to several days depending on environmental conditions. Some few cells are permanently arrested and never divide. Before a cell can begin mitosis and actually divide, it must replicate its DNA, synthesize some associated proteins, produce a supply of organelles sufficient for two daughter cells and assemble the machinery necessary for mitosis and cytokinesis. These things occur during the G1, S, and G2 phases of the cell cycle and are known collectively as interphase. The extremely important process of DNA replication occurs during the S phase (synthesis phase) of the cell cycle. Here also, many of the DNA-associated proteins are synthesized. G phases (gap phases) precede and follow the S phase. The G1 phase precedes the S phase and is a period of intense biochemical activity. The cell doubles in size, and its enzymes, ribosomes, mitochondria and other cytoplasmic molecules and structures also increase in number. Those cells that possess centrioles begin replicating here.

4 Mitochondria and chloroplasts, which are produced only from existing mitochondria and chloroplasts also increase their numbers. During the G2 phase, which follows the S phase and precedes mitosis, final preparation for cell division occurs. The newly replicated chromosomes, which are dispersed in the nucleus as very fine thread-like strands slowing begin to coil and condense into a compact form. Replication of centrioles if present, is completed during G2. Also during this period, the mitotic spindle apparatus begins to be assembled. Some cell types pass through successive cell cycles throughout the life of the organism. Other cell types occasionally divide; still others are permanently arrested and never divide. Division Rate Cells that do not divide after tissue is differentiated Cells that do not normally divide but can be stimulated to do so Cells that divide constantly and rapidly Cell Type Nerve cells Muscle cells Liver cells Skin cells Epithelial cells Sperm cells Bone marrow cells The stem cells in human blood marrow are a good example of cells that divide constantly and rapidly. The average red blood cell lives only about 120 days. There are about 2.5 trillion of them in an adult body. To maintain this number, about 2.5

5 million new red blood cells must be produced each second by the divison of stem cells. Mature red blood cells have no capacity to divide. Cells in the human liver do not normally divide in the adult. If, however, a portion of the liver is removed surgically, the remaining cells divide until the liver returns to its old size. Consider this-- all told, about 2 trillion cell divisions occur in an adult human every 24 hours; about 25 million a second! It is obviously of critical importance that various cell types divide at only a sufficient rate to produce the needed cells for growth and replacement. If any particular cell type divides more rapidly than is necessary, the normal organization and functions of the organism will be disrupted as specialized tissues are invaded and interfered with by the rapidly dividing cells. This is the course of events in a cancer. The function of mitosis is to maneuver replicated chromosomes such that daughter cells get their full complement. It does this by condensing chromosomes to compact structures and building a structure called the mitotic spindle. You should examine the structure of a chromosome so you can become acquainted with some of the nomenclature associated with it. By the beginning of mitosis, the chromosomes are pretty compact structures and under the light microscope are seen to be composed of two replicas, the chromatids. The chromatids are joined at a constricted region known as the centromere. Within the constricted region are protein-containing structures called kinetochores to which the microtubules of the mitotic spindle attach. When it is completely built, the mitotic spindle is a football shaped object consisting of two groups of microtubules: polar fibers, which reach from each pole to a central region of the

6 spindle and kinetochore fibers, which are attached to the kinetochores of the replicated chromosomes and reach to the poles. In those cells that have centrioles, each pole of the spindle gets one. Cells with centrioles contain a third group of shorter spindle fibers rhat radiate outward from the centriole and are collectively known as an aster. It is thought that the microtubules used in spindle construction are borrowed from the cytoskeleton of the cell and may be why dividing cells take on a characteristic rounded shape. The process of mitosis is conventionally divided into four phases: prophase metaphase anaphase telophase Of these, prophase is by far the longest. If a cell takes 10 minutes to divide, six of those minutes are spent in prophase. During prophase, the nucleolus disappears and as the chromosomes continue to condense, the nuclear envelope breaks down, dispersing as fragments much like endoplasmic reticulum. By the end of prophase, the chromosomes are fully condensed and are no longer separated from the cytoplasm. The polar fibers of the spindle are fully formed and the kinetochore fibers are attached to the kinetochore and also well-formed. A diagram is provided for you. During early metaphase, the chromatid pairs are moved about a

7 bit at the equatorial plane of the spindle. Finally, they become precisely arranged at the equatorial plane. A diagram is provided for you. At the beginning of anaphase, the two chromatids of each pair, until this point attached at the centromere, separate. This happens simultaneously for all chromatid pairs and the chromatids (now chromosomes) are rapidly moved toward their respective poles by kinetochore spindle fibers. A diagram is provided for you. By the beginning of telophase, the chromosomes have reached their opposite poles and the spindle apparatus begins to break down. A nuclear envelope reforms around each set of chromosomes and a nucleolus reappears. A diagram is provided for you. Cytokinesis, the division of cytoplasm, usually but not always accompanies mitosis. It is usually visible as a process that begins during telophase. Cytokinesis differs rather significantly in plants and animals. In animals, the plasma membrane begins to constrict at the equatorial plane of the old and vanishing spindle. At first a furrow appears; then a groove and finally like a purse-string, two daughter cells are pinched off. In plant cells, at the equatorial plane of the old, vanishing spindle, Golgi apparatus secrete vesicles containing precursors for the formation of a middle lamella. These coalesce to form a middle lamella and each daughter cell elaborates a cell wall against the middle lamella. Cancer is apparently the result of one or more cellular mutations or other persistent changes in the control of genetic expression. This is the only way to explain why, when a cancer

8 cell divides, the result is two cancer cells. Cancer facts: Cancer kills more children aged three to 14 than any other disease. Nearly 71 million Americans now living will get cancer eventually. For every 46 women that die of cancer, 54 men suffer the same fate. One out of every five deaths in America is a cancer death. There is no general epidemic of cancer, that is, no sudden dramatic rise in cancer incidence or mortality, as a whole, over the past 40 years except as indicated in the next item on this list. The most important absolute increases in cancer incidence and mortality during the past 40 years have been cancer of the lung, known to be caused largely by cigarette smoking. In 1992, the Centers for Disease Control said that 30 percent of all cancer deaths and 87 percent of all lung cancer deaths are attributable to tobacco use. The most important absolute decreases have occurred in cancer of the stomach and cervix. Cancer of the liver has also shown a steady decline. From: What is Cancer? You've heard of it of course but, "What, exactly, is cancer?" This section provides an introduction to what it is, how it starts, and how it spreads.

9 Cancer is the term we give to a large group of diseases that have one thing in common: abnormal cells growing out of control. Under normal circumstances, the number and growth of all our cells is a highly controlled mechanism. The body tells the cell when to divide and when to stop. But when the control signals in one of these cells goes wrong and its cell cycle becomes disturbed, it divides and divides. It continues on multiplying uncontrollably, making more and more of itself, and the result is a large group of cells called a tumor. This resulting tumor can be either benign or malignant. A benign tumor does not spread to other parts of the body and is rarely lifethreatening. Many breast lumps, for example, are benign tumors. A malignant tumor, however, can spread and can be deadly. When this tumor spreads, its malignant cells break off and travel through the blood system to other places in the body to settle and multiply, creating a new tumor called a secondary tumor. If the cancer has spread, doctors usually say it has 'metastasized'. The name given to the cancer, however, is based on where the cancer started, even if it has spread to other areas of the body. For example, even if lung cancer has spread to the liver it's still called lung cancer. How does it all start? What causes this uncontrollable multiplication of cells in the first place, as well as how fast it happens, differs from person to person. Cancer starts when one normal cell becomes cancerous. This happens when something disrupts its DNA, changing the instructions that control the cell cycle. In other words, the instructions that tell the cell how to grow, divide, and die have been disrupted. One or more of a variety of factors could cause this change, including diet, tobacco, sun, radiation, or certain chemicals. Certain factors, such as tobacco, have been proven to be associated with cancer and are thus called risk factors.

10 How do we treat Cancer? What Is Chemotherapy? Chemotherapy is the use of drugs to treat cancer. The drugs often are called "anti-cancer" drugs. It is very difficult for the drugs to tell the difference between normal human cells and cancer cells. Normal cells grow and die in a controlled way. But cancer occurs when cells become abnormal and keep dividing, forming more cells without stopping. Anticancer drugs destroy cancer cells by stopping growth or multiplication at some point in their cell cycle. In addition to chemotherapy, other methods sometimes are used to treat cancer. Your doctor may recommend that you have surgery to remove a tumor or to relieve certain symptoms that may be caused by your cancer. What Can Chemotherapy Achieve? Depending on the type of cancer and its stage of development, chemotherapy can be used: * To cure cancer. * To keep the cancer from spreading. * To slow the cancer's growth. * To kill cancer cells that may have spread to other parts of the body from the original tumor. To relieve symptoms that may be caused by the cancer. Does Chemotherapy Hurt? Getting chemotherapy by mouth, on the skin, or by injection generally feels the same as taking other medications by these methods. Having an IV started usually feels like drawing blood for a blood test. Some people feel a coolness or other unusual sensation in the area of the injection when the IV is started. Report such feelings to your doctor or nurse. Be sure that you also report any pain, burning, or discomfort that occurs during or after an IV treatment.

11 Will I lose my hair? The Chemotherapy drugs try to attack cells that are dividing. This kills the tumor cells, but also kills normal cells that are reproducing. Many chemotherapy drugs kill the cells that grow hair. This hair loss is not permanent. Almost all patients grow their hair back when the chemotherapy is finished. Reference the following animation how_the_cell_cycle_wor ks.html Then complete the quiz at the bottom of the page and me the results: Ariel.Haas@sduhsd.net

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