Part II Genetics
Cellular Reproduction
Chapter
8
Outline
	8.1	The Basics of Cellular Reproduction
	•	Cellular reproduction occurs as an organism becomes multicellular and as a tissue undergoes repair.112
	•	In order for cellular reproduction to occur, chromosomes must be condensed so that they can be distributed to daughter cells.113
	8.2	The Cell Cycle
	•	During interphase of the cell cycle, a cell duplicates its contents, including its chromosomes.114
	•	During the mitotic stage, a cell distributes its chromosomes to the daughter cells and divides the cytoplasm.114
	•	Cell division consists of mitosis and cytokinesis. Mitosis is division of the nucleus, and cytokinesis is division of the cytoplasm.114
	8.3	Mitosis and Cytokinesis
	•	Following mitosis, each daughter nucleus has the same number of chromosomes as the parent cell.115
	•	Once cytokinesis has occurred following mitosis, two daughter cells are present.118
 	8.4	The Cell Cycle Control System 
	•	The cell cycle is tightly controlled.119
	•	The cell cycle can stop due to external signals, such as contact inhibition, or internal, such as inappropriate telomere length.120
	•	A cell that is no longer in the cell cycle is in G0 or undergoes apoptosis, programmed cell death.120
	8.5	The Cell Cycle and Cancer
	•	The characteristics of cancer cells are associated with their ability to divide uncontrollably.121
	•	It is possible to avoid certain agents that contribute to the development of cancer and to take protective steps to reduce the risk of cancer.122–23
Many of our body tissues and organs can repair themselves if they become injured or damaged. This is because their cells are capable of undergoing mitosis, a process of nuclear division that enables cells and tissues to grow and be repaired. Exceptions are nerve cells, the cells that make up the nervous system. Injuries to the brain and spinal cord are very serious because nerve cells are designed to last a lifetime and do not ordinarily undergo mitosis. When nerve cells die, they are not likely to be replaced. The brain has approximately 35 billion nerve cells, and the loss of some of these is normal. However, in the case of brain injury or a condition such as Alzheimer disease, nerve cells die at a rapid rate, and brain function declines.
Scientists want to find a way to coerce differentiated nerve cells into undergoing mitosis. They also believe that human stem cells, which do divide, can be coaxed into becoming new nerve cells. Although the use of stem cells derived from human embryos is controversial and limited by legislation in the United States, adult stem cells are easily accessible in the bone marrow and already show promise of becoming nerve cells under the proper circumstances. All cells in the body of an organism have the same genetic composition, which explains why stem cells can potentially be used to form all cell types.
In this chapter, you will learn about the process of mitosis, how it is regulated, and what happens if it occurs either not at all or too frequently. 
8.1		The Basics of Cellular Reproduction
We humans, like other multicellular organisms, begin life as a single cell. In nine short months, however, we become trillions of cells because cellular reproduction has occurred over and over again. Even after we are born, cellular reproduction doesn’t stop—it continues as we grow (Fig. 8.1a), and when we are adults, it replaces worn-out or damaged tissues (Fig. 8.1b). Right now, your body is producing thousands of new red blood cells, skin cells, and cells that line your respiratory and digestive tracts. If you suffer a cut, cellular reproduction helps repair the injury.
Cellular reproduction is also necessary for the reproduction of certain organisms. When an amoeba splits, two new individual amoebas are produced. This process is called asexual reproduction because it doesn’t require a sperm and an egg (Fig. 8.1c). The next chapter concerns the production of egg and sperm, which are needed for sexual reproduction. 
One way to emphasize the importance of cellular reproduction is to say that “all cells come from cells.” You can’t have a new cell without a pre-existing cell, and you can’t have a new organism without a pre-existing organism (Fig. 8.1d). Cellular reproduction is necessary for the production of both new cells and new organisms. 
Chromosomes
Cellular reproduction always involves two important processes: growth and cell division. During growth, a cell duplicates the contents of its cytoplasm and its DNA. Then, during division, the cytoplasm and the DNA of the parent cell are distributed to the so-called daughter cells. (These terms have nothing to do with gender; they are simply a way to designate the beginning cell and the resulting cells.)	 
The passage of DNA to the daughter cells is critical because cells cannot continue to live without a copy of the genetic material. Especially in eukaryotic cells, passage of DNA to the daughter cells presents a problem because of the large quantity of DNA in the nucleus. For example, a human cell contains about 2 meters of DNA and a nucleus is only 5 to 8 micrometers (m) in diameter. During cellular reproduction, DNA is packaged into chromosomes, which allow DNA to be distributed to the daughter cells. A chromosome contains DNA, and it also contains proteins that help package the DNA and possibly function in utilizing the DNA as well. 
Chromatin to Chromosomes
When a eukaryotic cell is not undergoing cell division, the DNA and associated proteins have the appearance of thin threads called chromatin. Closer examination reveals that chromatin is periodically wound around a core of eight protein molecules so that it looks like beads on a string. The protein molecules are histones, and each bead is called a nucleosome (Fig. 8.2). 
Just before cell division occurs, the chromatin coils tightly into a fiber that has several nucleosomes to a turn. Then the fiber coils again before it loops back and forth and condenses to produce highly compacted chromosomes. Each species has a characteristic number of chromosomes; a human cell has 46 chromosomes. We can easily see chromosomes with a light microscope because just before division occurs a chromosome is 10,000 times more compact than is chromatin.
Another important event, that occurs in preparation for partition of chromosomes is DNA replication, when DNA makes a copy of itself. By the time we can clearly see the chromosomes, they are duplicated. A duplicated chromosome is composed of two identical halves called sister chromatids held together at a constricted region called a centromere. Each sister chromatid contains an identical DNA double helix.
8.2		The Cell Cycle
We have already indicated that cellular reproduction involves duplication of cell contents followed by cell division. For cellular reproduction to be orderly, you would expect the first event to occur before the second event, and that’s just what happens during the so-called cell cycle. The cell cycle is an orderly sequence of stages that takes place between the time a new cell has arisen from division of a parent cell to the point when it has given rise to two daughter cells. Duplication of cell contents occurs during the stage called interphase. 
Interphase
As Figure 8.3 shows, most of the cell cycle is spent in interphase. This is the time when a cell performs its usual functions, depending on its location in the body. The amount of time the cell takes for interphase varies widely. Some cells, such as nerve and muscle cells, typically remain in interphase and cell division is permanently arrested. These cells are said to have entered a G0 stage. Embryonic cells complete the -entire cell cycle in just a few hours. In contrast, interphase alone in a rapidly dividing mammalian cell, such as an adult stem cell, may last for about 20 hours, which is 90% of the cell cycle.
DNA replication occurs in the middle of interphase and serves as a way to divide interphase into three stages: G1, S, and G2. G1 is the stage before DNA replication, and G2 is the stage following DNA synthesis. Originally, G stood for “gap,” but now that we know how metabolically active the cell is, it is better to think of G as standing for “growth.” Protein synthesis is very much a part of these growth stages.
During G1, a cell doubles its organelles (such as mitochondria and ribosomes) and accumulates materials that will be used for DNA replication. Following G1, the cell enters the S stage. The S stands for synthesis, and certainly DNA synthesis is required for DNA replication. At the beginning of the S stage, each chromosome has one DNA double helix. At the end of this stage, each chromosome is composed of two sister chromatids, each having one double helix. Another way of expressing these events is to say that DNA replication  results in duplicated chromosomes.
Following the S stage, G2 is the stage that extends from the completion of DNA replication to the onset of mitosis. During this stage, the cell synthesizes proteins that will be needed for cell division, such as the protein found in microtubules. The role of microtubules in cell division is described in a later section.
M (Mitotic) Stage
Cell division occurs during the M stage, which encompasses both division of the nucleus and division of the cytoplasm. The type of nuclear division associated with the cell cycle is called mitosis, which accounts for why this stage is called the M stage. As a result of mitosis, the daughter nuclei are identical to the parent cell and to each other—they all have the same number and kinds of chromosomes. Division of the cytoplasm, which starts even before mitosis is finished, is called cytokinesis. 
8.3		Mitosis and Cytokinesis
Each sister chromatid of a duplicated chromosome carries the same genetic information because its DNA double helix has the same sequence of base pairs as did the original chromosome. Thus, it is proper, once the chromatids have separated, to call them daughter chromosomes (Fig. 8.4). Because each original chromosome goes through the same process of DNA replication followed by separation of the chromatids to form daughter chromosomes, the daughter nuclei produced by mitosis are genetically identical to each other and to the parent nucleus. In the simplest of terms, if the parent nucleus has 4 chromosomes, each daughter nucleus also has 4 chromosomes of exactly the same type. One way to keep track of the number of chromosomes in drawings is to count the number of centromeres, because every chromosome has a centromere. 
Every animal has an even number of chromosomes because each parent contributed half of the chromosomes to the new individual. In drawings of mitosis, some chromosomes are colored red and some are colored blue to represent that half of the chromosomes are derived from those contributed by one parent and the other half are derived from chromosomes from the other parent.
The Spindle 
While it may seem easy to separate the chromatids of only 4 duplicated chromosomes, imagine the task when there are 46 chromosomes, as in humans, or 78, as in dogs. Certainly it is helpful that chromosomes be highly condensed before the task begins, but clearly some mechanism is needed to complete separation in an organized manner. Most eukaryotic cells rely on a spindle, a cytoskeletal structure, to pull the chromatids apart. A spindle has spindle fibers made of microtubules that are able to assemble and disassemble. First, the microtubules assemble to form the spindle that takes over the center of the cell and separates the chromatids. Later, they disassemble.
A centrosome is the primary microtubule organizing center of a cell. Centrosome duplication occurs at the start of the S phase of the cell cycle and is completed by G2. During the first part of the M stage, the centrosomes separate and move to opposite sides of the nucleus, where they form the poles of the spindle. As the nuclear envelope breaks down, spindle fibers take over the center of the cell. Certain ones overlap at the spindle equator, which is midway between the poles. Others attach to duplicated chromosomes in a way that ensures the separation of the sister chromatids and their proper distribution to the daughter cells. Whereas the chromosomes will be inside the newly formed daughter nuclei, a centrosome will be just outside.
Traditionally, mitosis is divided into a sequence of events, even though it is a continuous process. We will describe mitosis as having four phases: prophase, metaphase, anaphase, and telophase. These phases are labeled in Figure 8.5 for a dividing plant nucleus. Plant cells have centrosomes but they are not clearly visible especially because they lack centrioles. In an animal cell, each centrosome has two centrioles and an array of microtubules called an aster. Otherwise the descriptions on the next two pages apply to both animal and plant cells.
Phases of Mitosis in Animal Cells
Separation of chromatids during mitosis requires the phases listed on the previous page and described in Figure 8.6. Although mitosis is divided into these phases, it is a continuous process. Before studying the descriptions of these phases in Figure 8.6, recall that before mitosis begins, DNA has replicated. Each double helix is located in a chromatid; therefore, the chromosomes consist of sister chromatids attached at a centromere. Notice that some chromosomes are colored red and some are colored blue. The red chromosomes were inherited from one parent and the blue chromosomes from the other parent.
During mitosis, a spindle arises that will separate the sister chromatids of each duplicated chromosome. Once separated, the sister chromatids become daughter chromosomes. In this way, the resulting daughter nuclei are identical to each other and to the parental nucleus. In Figure 8.6, the daughter nuclei not only have four chromosomes; they each have one red short, one blue short, one red long, and one blue long, the same as the mother cell had.
Mitosis is usually followed by division of the cytoplasm, or cytokinesis. Cytokinesis begins during telophase and continues after the nuclei have formed in the daughter cells. The cell cycle is now complete, and the daughter cells enter interphase, during which the cell will grow and DNA will replicate once again. In rapidly dividing mammalian stem cells, the cell cycle lasts for 24 hours. Mitosis and cytokinesis require only one hour of this time period.
Cytokinesis in Animal and Plant Cells
Cytokinesis accompanies mitosis in most cells but not all. When mitosis occurs but cytokinesis doesn’t occur, the result is a multinucleated cell. For example, skeletal muscle cells in vertebrate animals and the embryo sac in flowering plants are multinucleated.
Cytokinesis in Animal Cells
In animal cells, a cleavage furrow, which is an indentation of the membrane between the two daughter nuclei, begins as anaphase draws to a close. The cleavage furrow deepens when a band of actin filaments, called the contractile ring, slowly forms a circular constriction between the two daughter cells. The action of the contractile ring can be likened to pulling a drawstring ever tighter about the middle of a balloon. A narrow bridge between the two cells is visible during telophase, and then the contractile ring continues to separate the cytoplasm until there are two independent daughter cells (Fig. 8.7).
Cytokinesis in Plant Cells
Cytokinesis in plant cells occurs by a process different from that seen in animal cells (Fig. 8.8). The rigid cell wall that surrounds plant cells does not permit cytokinesis by furrowing. Instead, cytokinesis in plant cells involves the building of new plasma membrane and cell walls between the daughter cells.
Cytokinesis is apparent when a small, flattened disk appears between the two daughter plant cells. In electron micrographs, it is possible to see that the disk is composed of vesicles. The Golgi apparatus produces these vesicles, which move along microtubules to the region of the disk. As more vesicles arrive and fuse, a cell plate can be seen. The cell plate is simply newly formed plasma membrane that expands outward until it reaches the old plasma membrane and fuses with it. The new membrane releases molecules that form the new plant cell walls. These cell walls are later strengthened by the addition of cellulose -fibrils. 
8.4		The Cell Cycle Control System 
In order for a cell to reproduce successfully, the cell cycle must be controlled. The importance of cell cycle control can be appreciated by comparing the cell cycle to the events that occur in an automatic washing machine. The washer’s control system starts to wash only when the tub is full of water, doesn’t spin until the water has been emptied, delays the most vigorous spin until rinsing has occurred, and so forth. Similarly, the cell cycle’s control system ensures that the G1, S, G2, and M stages occur in order and only when the previous stage has been successfully completed. 
Cell Cycle Checkpoints
Just as a washing machine will not begin to agitate the load until the tub is full, the cell cycle has checkpoints that can delay the cell cycle until all is well. The cell cycle has many checkpoints, but we will consider only three: G1, G2 and the mitotic checkpoint (Fig. 8.9). 
The G1 checkpoint is especially significant because if the cell cycle passes this checkpoint, the cell is committed to divide. If the cell does not pass this checkpoint, it can enter G0, during which it performs specialized functions but does not divide. If the DNA is damaged beyond repair, the internal signaling protein p53 can stop the cycle at this checkpoint. First, p53 attempts to initiate DNA repair, but if that is not possible, it brings about the death of the cell by apoptosis (see Fig. 8.11).
The cell cycle hesitates at the G2 checkpoint ensuring that DNA has replicated. This prevents the initiation of the M stage unless the chromosomes are duplicated. Also, if DNA is damaged, as from exposure to solar radiation or X rays, arresting the cell cycle at this checkpoint allows time for the damage to be repaired so that it is not passed on to daughter cells.
Another cell cycle checkpoint occurs during the mitotic stage. The cycle hesitates to make sure the chromosomes are going to be distributed accurately to the daughter cells. The cell cycle does not continue until every chromosome is ready for the nuclear division process. 
Internal and External Signals
The checkpoints of the cell cycle are controlled by internal and external signals. A signal is a molecule that stimulates or inhibits an event. Signals outside the cell are called external signals and those inside the cell are called internal signals. Inside the cell, enzymes called kinases remove phosphate from ATP and add it to another molecule. Just before the S stage, a protein called S-cyclin combines with a kinase called S-kinase, and synthesis of DNA takes place. Just before the M stage, M-cyclin combines with a kinase called M-kinase, and mitosis occurs. Cyclins are so named because their quantity is not constant. They increase in amount until they combine with a kinase, but this is a suicidal act. The kinase not only activates a protein that drives the cell cycle, but it also activates various enzymes, one of which destroys the cyclin (Fig. 8.10).
Some external signals, such as growth factors and hormones, stimulate cells to go through the cell cycle. An animal and its organs grow larger if the cell cycle occurs. Growth factors also stimulate repair of tissues. Even cells that are arrested in G0 will finish the cell cycle if stimulated to do so by growth factors. For example, epidermal growth factor (EGF) stimulates skin in the vicinity of an injury to finish the cell cycle, thereby repairing the damage. 
Hormones act on tissues at a distance, and some signal cells to divide. For example, at a certain time in the menstrual cycle of females, the hormone estrogen stimulates cells lining the uterus to divide and prepare the lining for implantation of a fertilized egg.
The cell cycle can be inhibited by cells coming into contact with other cells, and by the shortening of chromosomes. In cell culture, cells will divide until they line a container in a one-cell-thick sheet. Then they stop dividing, a phenomenon termed contact inhibition. Researchers are beginning to discover the external signals that result in this inhibition. Some years ago, it was noted that mammalian cells in cell culture divide about 70 times, and then they die. Cells seem to “remember” the number of times they divided before, and stop dividing when the usual number of cell divisions is reached. It’s as if senescence, the aging of cells, is dependent on an internal battery-operated clock that winds down and then stops. We now know that senescence is due to the shortening of telomeres. A telomere is a repeating DNA base sequence (TTAGGG) at the end of the chromosomes that can be as long as 15,000 base pairs. Telomeres have been likened to the protective caps on the ends of shoelaces. Rather than keeping chromosomes from unraveling, however, telomeres stop chromosomes from fusing to each other. Each time a cell divides, some portion of a telomere is lost; when telomeres become too short, the chromosomes fuse and can no longer duplicate. Then the cell is “old” and dies by a process called apoptosis.
Apoptosis
Apoptosis is often defined as programmed cell death because the cell progresses through a typical series of events that bring about its destruction (Fig. 8.11). The cell rounds up and loses contact with its neighbors. The nucleus fragments, and the plasma membrane develops blisters. Finally, the cell breaks into fragments, and its bits and pieces are engulfed by white blood cells and/or neighboring cells. A remarkable finding of the past few years is that cells routinely harbor the enzymes, now called caspases, that bring about apoptosis. These enzymes are ordinarily held in check by inhibitors, but are unleashed by either internal or external signals. 
Cell division and apoptosis are two opposing processes that keep the number of cells in the body at an appropriate level. In other words, cell division increases, and apoptosis decreases, the number of somatic cells (body cells). Both the cell cycle and apoptosis are normal parts of growth and development. An organism begins as a single cell that repeatedly undergoes the cell cycle to produce many cells, but eventually some cells must die in order for the organism to take shape. For -example, when a tadpole becomes a frog, the tail disappears as apoptosis occurs. In humans, the fingers and toes of an embryo are at first webbed, but later they are freed from one another as a result of apoptosis.
Apoptosis occurs all the time, particularly if an abnormal cell that could become cancerous appears. Death through apoptosis prevents a tumor from developing.
8.5		The Cell Cycle and Cancer
Cancer is a disease of the cell cycle, in that the cell cycle is out of control, and cellular reproduction occurs repeatedly without end. Cancers are classified according to their location. Carcinomas are cancers of the epithelial tissue that lines organs; sarcomas are cancers arising in muscle or connective tissue (especially bone or cartilage); and leukemias are cancers of the blood. A high rate of cell division makes a tissue susceptible to cancer because it increases the chances of a mutation (change in DNA base sequence) that causes a cell to divide uncontrollably or to ignore apoptosis signals. In this chapter, we consider some general characteristics of cancer cells. Chapter 12 explores specific changes that lead to cancerous growth.
Characteristics of Cancer Cells
Carcinogenesis, the development of cancer, is gradual; it may be decades before a tumor is visible. Cancer cells then have these characteristics:
Cancer cells lack differentiation. Cancer cells are nonspecialized and do not contribute to the functioning of a body part. A cancer cell does not look like a differentiated epithelial, muscle, nervous, or connective tissue cell; instead, it looks distinctly abnormal. As mentioned, normal cells can enter the cell cycle about 70 times, and then they die. Cancer cells can enter the cell cycle repeatedly, and in this way they are immortal.
Cancer cells have abnormal nuclei. The nuclei of cancer cells are enlarged and may contain an abnormal number of chromosomes. The chromosomes are also abnormal; some parts may be duplicated, or some may be deleted. In addition, gene amplification (extra copies of specific genes) is seen much more frequently than in normal cells. Ordinarily, cells with damaged DNA undergo apoptosis, but cancer cells fail to undergo apoptosis even though they are abnormal.
Cancer cells form tumors. Normal cells anchor themselves to a substratum and/or adhere to their neighbors. Then, they exhibit contact inhibition and stop dividing. Cancer cells, on the other hand, have lost all restraint; they pile on top of one another and grow in multiple layers, forming a tumor. They have a reduced need for growth factors, and they no longer respond to inhibitory signals. As cancer develops, the most aggressive cell becomes the dominant cell of the tumor.
Cancer cells promote angiogenesis and undergo metastasis. A benign tumor is usually encapsulated and, therefore, will never invade adjacent tissue. Cancer in situ is a tumor in its place of origin, but it is not encapsulated and will eventually invade surrounding tissues. Cancer cells produce enzymes that allow tumors to invade underlying tissues. Invasive tumors produce cancer cells that travel through the blood and lymph to start tumors elsewhere in the body. Malignancy is present once metastasis has established new metastatic tumors distant from the primary tumor (Fig. 8.12).
Angiogenesis, the formation of new blood vessels, is required to bring nutrients and oxygen to a cancerous tumor. Some modes of cancer treatment are aimed at preventing angiogenesis from occurring.
The patient’s prognosis (probable outcome) is depen-dent on (1) whether the tumor has invaded surrounding tissues, and (2) whether there are metastatic tumors in distant parts of the body. 
Cancer Treatment
Cancer treatments either remove the tumor or interfere with the ability of cancer cells to reproduce. For many solid tumors, removal by surgery is often the first line of treatment. When the cancer is detected at an early stage, surgery may be sufficient to cure the patient by removing all cancerous cells. 
Because cancer cells are rapidly dividing, they become susceptible to radiation therapy and chemotherapy (Fig. 8.13). The goal of radiation is to kill cancer cells within a specific tumor by directing high-energy beams at the tumor. DNA is damaged to the point that replication can no longer occur, and the cell undergoes apoptosis. Chemotherapy is a way to kill cancer cells that have spread throughout the body. Like radiation, most chemotherapeutic drugs lead to the death of cells by damaging their DNA or interfering with DNA synthesis. Others interfere with the functioning of the mitotic spindle. The drug vinblastine, first obtained from a flowering plant called the periwinkle, prevents the spindle from forming. Taxol, extracted from the bark of the Pacific yew tree, prevents the spindle from functioning as it should. Unfortunately, radiation and chemotherapy often damage cells other than cancer cells, leading to side effects such as nausea and hair loss. 
Hormonal therapy also prevents cell division but in a different way. These drugs are designed to prevent cancer cell growth by preventing the cells from receiving signals necessary for their continued growth and division. For example, the drug tamoxifen modifies the receptor for estrogen so that this hormone cannot bind to it and promote the cell cycle. Other drug therapies are also being investigated. One proposed therapy that is now well under way uses antiangiogenic drugs designed to inhibit angiogenesis by breaking up the network of capillaries in the vicinity of the tumor. Having its blood supply reduced confines and reduces a tumor.
Prevention of Cancer
Evidence is clear that the risk of certain types of cancer can be reduced by adopting protective behaviors and following recommended dietary guidelines. 
Protective Behaviors
To prevent the development of cancer, people are advised to avoid smoking, sunbathing, and excessive alcohol consumption. 
Cigarette smoking accounts for about 30% of all cancer deaths. Smoking is responsible for 90% of lung cancer cases among men and 79% among women—about 87% altogether. People who smoke two or more packs of cigarettes a day have lung cancer mortality rates 15 to 25 times greater than those of nonsmokers. Smokeless tobacco (chewing tobacco or snuff) increases the risk of cancers of the mouth, larynx, throat, and esophagus.
Skin cancers are considered sun-related. Sun exposure is a major factor in the development of the most dangerous type of skin cancer, melanoma, and the incidence of this cancer increases in people living near the equator. Similarly, excessive radon gas1 exposure in homes increases the risk of lung cancer, especially in cigarette smokers. It is best to test your home and, if necessary, take the proper remedial actions.
Cancers of the mouth, throat, esophagus, larynx, and liver occur more frequently among heavy drinkers, especially when accompanied by tobacco use (cigarettes, cigars, or chewing tobacco).
Protective Diet
The risk of cancer (especially colon, breast, and uterine cancers) is 55% greater among obese women and 33% greater among obese men, compared to people of normal weight. Weight loss in these groups can therefore reduce cancer risk. In addition, the following dietary guidelines are recommended (Fig. 8.14):
	•	Increase consumption of foods that are rich in vitamins A and C. Beta-carotene, a precursor of vitamin A, is found in dark green leafy vegetables, carrots, and various fruits. Vitamin C is present in citrus fruits. These vitamins are called antioxidants because in cells they prevent the formation of free radicals (organic ions having an unpaired electron) that can possibly damage DNA. Vitamin C also prevents the conversion of nitrates and nitrites into carcinogenic nitrosamines in the digestive tract.
	•	Avoid salt-cured or pickled foods because they may increase the risk of stomach and esophageal cancers. Smoked foods, such as ham and sausage, contain chemical carcinogens similar to those in tobacco smoke. Nitrites are sometimes added to processed meats (e.g., hot dogs and cold cuts) and other foods to protect them from spoilage; as mentioned, nitrites are sometimes converted to cancer-causing nitrosamines in the digestive tract.
	•	Include in the diet vegetables from the cabbage family, which includes cabbage, broccoli, brussels sprouts, kohlrabi, and cauliflower. Consuming these vegetables may reduce the risk of gastrointestinal and respiratory tract cancers.
The Chapter in Review
Summary
8.1		The Basics of Cellular Reproduction
Cellular reproduction occurs when growth and repair of tissues take place. Cellular reproduction is also necessary to both asexual and sexual reproduction. Following fertilization, a single cell becomes a multicellular organism by cellular reproduction.
When a cell is not dividing, chromatin looks like beads on a string because DNA (the string) is wound around histones. The bead is called a nucleosome. Just before cell division, duplicated chromatin condenses to form duplicated chromosomes consisting of two chromatids held together at a centromere. During cell division, one-half of the cytoplasm and a copy of the cell’s DNA are passed on to each of two daughter cells.
8.2		The Cell Cycle
The cell cycle consists of interphase and the M (mitotic) stage:
Interphase has the following stages:
	•	G1The cell doubles its organelles and accumulates materials that will be used for DNA replication. 
	•	SDNA replicates.
	•	G2The cell synthesizes proteins that will be needed for cell division. 
The M (mitotic) stage consists of mitosis and cytokinesis. As a result of mitosis, the daughter nuclei are genetically identical to the parent nucleus and to each other. If the parent nucleus has 4 chromosomes, the daughter nuclei each have 4 chromosomes.
8.3		Mitosis and Cytokinesis 
Cell division consists of mitosis and cytokinesis. 
Mitosis
Mitosis has four phases: 
	•	During prophase, the chromosomes are condensing. Outside the nucleus, the spindle begins to assemble between the separating centrosomes. Prophase continues with the disappearance of the nucleolus and the breakdown of the nuclear envelope. Spindle microtubules from each pole attach to the chromosomes in the region of a centromere.
	•	During metaphase, the chromosomes are aligned at the spindle equator midway between the spindle poles. 
	•	During anaphase, the sister chromatids separate and become daughter chromosomes. As the microtubules attached to the chromosomes disassemble, each pole receives a set of daughter chromosomes. 
	•	During telophase, the spindle disappears as new nuclear envelopes form around the daughter chromosomes. Each nucleus contains the same number and kinds of chromosomes as the original parent nucleus. Division of the cytoplasm begins. 
Cytokinesis
Cytokinesis differs for animal and plant cells. 
	•	In animal cells, a furrowing process involving actin filaments divides the cytoplasm. 
	•	In plant cells, a cell plate forms from which the plasma membrane and cell wall develop. 
8.4		The Cell Cycle Control System
Checkpoints are interacting signals that promote or inhibit the continuance of the cell cycle. Important checkpoints include these three:
	•	At G1, the cell can enter G0 or undergo apoptosis if DNA is damaged beyond repair. If the cell cycle passes this checkpoint, the cell is committed to complete the cell cycle. 
	•	At G2, the cell checks to make sure DNA has replicated properly. 
	•	At the mitotic checkpoint, the cell makes sure the chromosomes are ready to be partitioned to the daughter cells. 
Both internal and external signals converge on checkpoints to control the cell cycle. Cyclin-kinase complexes are internal signals that promote either DNA replication or mitosis. Growth factors and hormones are external signals that promote the cell cycle in connection with growth. Inhibitory external signals are responsible for contact inhibition. Internally, when telomeres are too short, the cell cycle stops because the chromosomes fuse together. 
When DNA cannot be repaired, apoptosis occurs as enzymes called caspases bring about destruction of the nucleus and the rest of the cell. 
8.5		The Cell Cycle and Cancer
Cancer cells are undifferentiated, divide repeatedly, have abnormal nuclei, do not require growth factors, and are not constrained by their neighbors. After forming a tumor, cancer cells metastasize and start new tumors elsewhere in the body. Certain behaviors, such as avoiding smoking and sunbathing and adopting a diet rich in fruits and vegetables, are protective against cancer. 
Thinking Scientifically
	1.	The survivors of the atomic bombs that were dropped on Hiroshima and Nagasaki have been the subjects of long-term studies of the effects of ionizing radiation on cancer incidence. The frequencies of different types of cancer in these individuals varied across the decades. In the 1950s, high levels of leukemia and cancers of the lung and thyroid gland were observed. The 1960s and 1970s brought high levels of breast and salivary gland cancers. In the 1980s, rates of colon cancer were especially high. Why do you suppose the rates of different types of cancer varied across time?
	2.	During prophase of mitosis, the nuclear membrane breaks down. This is undoubtedly a complex, energy-consuming process that has to be carried out again, in reverse, at the end of mitosis. Why do you suppose the nuclear membrane must break down at the beginning of mitosis? What mechanism can you envision for the dismantling of the nuclear membrane?
Testing Yourself
Choose the best answer for each question.
	1.	A chromosome contains
	a. DNA and RNA.
	b. DNA and protein.
	c. DNA only.
	d. DNA, RNA, and protein. 
	2.	The two identical halves of a duplicated chromosome are called
	a. chromosome arms.
	b. nucleosomes.
	c. chromatids.
	d. homologues.
For questions 3–6, match the items to those in the key. Answers can be used more than once.
Key:
	a. G1 stage of interphase
	b. G2 stage of interphase
	c. S stage of interphase 
	3.	This stage follows mitosis.
	4.	DNA is replicated during this stage.
	5.	Organelles are doubled in number during this stage.
	6.	During this stage, the cell produces proteins that will be needed for cell division.
	7.	Label the stages and phases of the cell cycle on the following diagram. Include anaphase, cytokinesis, G1, G2, metaphase, prophase, S, and telophase.
For questions 8–13, match the items to those in the key. Answers can be used more than once, and each question can have more than one answer.
Key:
	a. prophase
	b. metaphase
	c. anaphase
	d. telophase
	8.	The nucleolus disappears, and the nuclear membrane breaks down.
	9.	The spindle disappears, and the nuclear envelope forms.
	10.	Sister chromatids separate.
	11.	Spindle poles move apart as spindle fibers slide past each other.
	12.	Chromosomes are aligned on the spindle equator.
	13.	Each chromosome is composed of two sister chromatids.
	14.	Plants cannot use a cleavage furrow to undergo cytokinesis because they
	a. lack a plasma membrane.
	b. have a cell wall.
	c. have too many chromosomes.
	d. are too small. 
	15.	Which DNA checkpoint allows damaged DNA to be repaired before it is passed on to daughter cells?
	a. G1
	b. G2
	c. S
	d. mitotic
	16.	Which of the following is not an event of apoptosis?
	a. loss of contact with neighboring cells
	b. blistering of the plasma membrane
	c. increase in the number of mitochondria
	d. fragmentation of the nucleus
	17.	Which of the following is not a feature of cancer cells?
	a. exhibit contact inhibition
	b. have enlarged nuclei
	c. stimulate the formation of new blood vessels
	d. are capable of traveling through blood and lymph
	18.	The spindle begins to assemble during
	a. prophase.
	b. metaphase.
	c. anaphase.
	d. interphase.
	19.	Which is not one of the mitotic stages?
	a. anaphase
	b. telophase
	c. interphase
	d. metaphase
	20.	What is the checkpoint for the completion of DNA synthesis?
	a. G1
	b. S
	c. G2
	d. M
	21.	Programmed cell death is called
	a. mitosis.
	b. meiosis.
	c. cytokinesis.
	d. apoptosis.
	22.	In human beings, mitosis is necessary for
	a. growth and repair of tissues.
	b. formation of the gametes.
	c. maintaining the chromosome number in all body cells.
	d. the death of unnecessary cells.
	e. Both a and c are correct.
	23.	In which phase of mitosis is evidence of cytokinesis present?
	a. prophase
	b. metaphase
	c. anaphase
	d. telophase
	e. Both c and d are correct.
	24.	Which of these is not a behavior that could help prevent cancer?
	a. maintaining a healthy weight
	b.	
eating more dark green leafy vegetables, carrots, and various fruits
	c. not smoking
	d.	
maintaining estrogen levels through hormone replacement therapy
	e. consuming alcohol only in moderation 
Go to www.mhhe.com/maderessentials for more quiz questions.
Bioethical Issue
Embryonic stem cells are cells from young embryos which divide indefinitely. They are of interest to researchers because they are undifferentiated and have the ability to develop into a variety of cell types, including brain, heart, bone, muscle, and skin cells. They can help scientists to understand how cells change as they mature. In addition, they offer the hope of curing cell-based diseases such as diabetes, Parkinson’s disease, and heart disease. Embryonic stem cell research involves the destruction of human embryos. Opponents of this research argue that embryos should not be destroyed because they have the same rights as all human beings. Proponents counter that the embryos used for research are excess embryos from in vitro fertilization procedures, and they would be destroyed anyway. Therefore, they should be used to alleviate human suffering. Do you think that human embryos should be used for stem cell research?
Understanding the Terms
anaphase115
angiogenesis121
apoptosis120
aster115
cancer121
carcinogenesis121
cell cycle114
cell plate118
centromere113
centrosome115
checkpoint119
chromatin113
chromosome113
contact inhibition120
cyclin119
cytokinesis114
DNA replication113
histone113
interphase114
kinase119
metaphase115
metastasis121
mitosis114
nucleosome113
prophase115
signal119
sister chromatid113
somatic cell120
spindle115
spindle equator115
telomere120  
telophase115
tumor121
Match the terms to these definitions:
a. _______________ The protein molecules in nucleosomes.
b. _______________ Chromatids are held together at this constricted region of a chromosome.
c. _______________ Component of the cytoskeleton that pulls chromatids apart.
d. _______________ Microtubules are organized in this region of a cell.
e. _______________ A molecule that stimulates or inhibits an event. 

The brain has 35 
billion nerve cells—but when these cells die (green), they are not replaced.
Cancer is characterized by the over-division of cells.
Heart attacks are caused by the death of cardiac muscle cells.
Figure 8.1Cellular reproduction.

Figure 8.3The cell cycle. 
Cells go through a cycle that consists of four stages: G1, S, G2, and M. The major activity for each stage is given. Some cells can exit G1 and enter a G0 stage.
Figure 8.6Phases of mitosis in animal cells.
The red chromosomes were inherited from one parent and the blue chromosomes from the other parent.
Figure 8.8Cytokinesis in plant cells.
During cytokinesis in a plant cell, a cell plate forms midway between two daughter nuclei and extends to the original plasma membrane.
Figure 8.7Cytokinesis in animal cells.
A single cell becomes two cells by a furrowing process. A cleavage furrow appears as early as anaphase, and a contractile ring, composed of actin filaments, gradually gets smaller until there are two cells.
Copyright by R. G. Kessel and C. Y. Shih, Scanning Electron Microscopy in Biology: 
A Students’ Atlas on Biological Organization, Springer-Verlag, 1974.
Figure 8.11Apoptosis.
Apoptosis is a sequence of events that results in a fragmented cell. The fragments are phagocytized by white blood cells and neighboring tissue cells.
Figure 8.13Cancer cells.
This micrograph contrasts cancer cells with normal cells.
Figure 8.12Development of breast cancer.
a. Breast cancer begins as a cancer in situ. The tumor may become invasive and invade lymphatic or blood vessels. Metastasis occurs when new metastatic tumors occur some distance from the original tumor. b. A mammogram (X-ray image of the breast) can find a tumor (circled) too small to be felt.
Figure 8.10Internal signals of the cell cycle.
S-cyclin must combine with S-kinase for the cell cycle to begin DNA replication. M-cyclin must combine with M-kinase for the cell cycle to start mitosis.
Figure 8.9Cell cycle checkpoints.
Internal and external signals determine whether the cell is ready to proceed past cell cycle checkpoints. Three important checkpoints are designated.
Figure 8.6Phases of the mitosis in animal cells—continued.
Figure 8.5Mitosis in a plant cell.
The chromosomes are stained blue, and microtubules of the spindle fibers are stained pink in these photos of a dividing African blood lily. For a description of these phases see Figure 8.6.
Figure 8.4Overview of mitosis.
Counting the number of centromeres tells you the number of chromosomes.
Figure 8.2Levels of chromosome organization.
Histones are responsible for packaging chromatin so that it fits into the nucleus and so that it becomes highly condensed when cell division occurs. 
Check Your Progress
	1.	When does cellular reproduction occur in an animal?
	2.	In what ways is cellular reproduction necessary to the continued existence of a mature organism and the production of a new organism?
	3.	Contrast the appearance of chromatin with a chromosome that is ready to undergo cellular reproduction.
Answers:1. When an animal grows, and when tissues are repaired.2. Mature organisms have to replenish worn out cells and repair injuries. Unicellular organisms divide in order to reproduce, and multicellular organisms develop from a single cell.3. Chromatin is less condensed than a chromosome, and its DNA is not duplicated. A chromosome ready to undergo cellular reproduction is condensed and is duplicated.
Check Your Progress
	1.	
During what stage of the cell cycle does DNA replicate? What does a chromosome look like following DNA replication?
	2.	What happens during the M stage of the cell cycle?
Answers: 1. DNA replication occurs during the S stage of the cell cycle.Following replication, the chromosomes are composed of two sister chromatids held together at a centromere.2. Mitosis (nuclear division in which the chromosome number stays constant) and cytokinesis (division of cytoplasm) occur.
Check Your Progress
List the major protective strategies you can employ to reduce your risk of cancer.
Answer: Avoid tobacco use, reduce sun exposure, reduce radon exposure, avoid heavy drinking, avoid obesity, consume foods rich in vitamins A and C, avoid chemically preserved foods, and include vegetables from the cabbage family in your diet.
Check Your Progress
	1.	During what phase of mitosis are duplicated chromosomes aligned at the spindle equator?
	2.	
During what phase of mitosis are daughter chromosomes moving toward the spindle poles? 
Answers:1. Metaphase.2. Anaphase.
Check Your Progress
What explanation can you give for the differences in cytokinesis between plant cells and animal cells? 
Answer:The rigid cell wall of plant cells does not permit cytokinesis by furrowing as in animal cells.
Check Your Progress
	1.	
Explain the significance of checkpoints in the cell cycle.
	2.	
What is a signal, and in general what two kinds of signals control the cell cycle?
Answers:1. It is important for each step of the cycle to be completed correctly before the next one begins, and checkpoints allow the cell to make sure that happens.2. A signal is a molecule that promotes or inhibits an event. Internal and external signals control the cell cycle.
Check Your Progress
	1.	Describe how cancer relates to the cell cycle.
	2.	
List the characteristic features of cancer cells.
	3.	
Contrast the modes of action of radiation and chemotherapy with the mode of action of hormonal therapy. 
Answers:1. Cancer occurs when the cell cycle is not regulated properly.
2. Nondifferentiated cells; abnormal nuclei; tumor formation; promote angiogenesis and undergo metastasis. 3. Radiation and chemotherapy damage DNA or otherwise interfere with the completion of mitosis. Hormonal therapy interferes with cell’s reception of an external signal to divide.
b. Mammogram showing tumor.
1Radon gas results from natural radioactive breakdown of uranium in soil, rocks, and water.
Cellular reproduction occurs (a) when small children grow to be adults and also (b) when mature organisms repair their tissues. Cellular reproduction also occurs when (c) unicellular organisms reproduce, and (d) when zygotes, the product of sperm and egg fusion, develop into multicellular organisms capable of independent existence. 
Figure 8.14The right diet helps prevent cancer.
Foods that help protect against cancer include fruits and dark green leafy vegetables, including swiss chard (left), which are rich in vitamins A and C, and vegetables from the cabbage family, including broccoli.