Cell Division and CancerYou 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. 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 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:
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. 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.
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 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:
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 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. Most multicellular eukaryotic organisms reproduce sexually. Sexual reproduction always involves two events:
Fertilization is the means by which the different parent contributions of genetic information are brought together. Meiosis is a special kind of nuclear division that is believed to have evolved from mitosis. To understand meiosis, we need to consider chromosomes and their numbers. Every organism has a chromosome number characteristic of its particular species. Each somatic (body) cell in corn has 20 chromosomes; in a cat one finds 38; in a human 46; in a goldfish, 94. Sex cells or gametes have exactly half the number of chromosomes characteristic of the somatic cells of the organism. The number of chromosomes in the gametes is referred to as the haploid number. And, as you might know, the number of chromosomes in somatic cells is referred to as the diploid number. Cells that have more than two sets of chromosomes are said to be polyploid. Polyploidy is fairly rare in the animal kingdom but fairly common in the plant kingdom. In shorthand, the haploid number is often referred to as n and the diploid number 2n. When a sperm fertilizes an egg, two haploid nuclei fuse, n + n = 2n and the diploid number is restored. A diploid cell produced by the fusion of two gametes is known as a zygote. In every diploid cell, each chromosome has a partner. These pairs of chromosomes are known as homologous pairs or homologs. The two resemble each other in size and shape and in genetic information but they are not identical. One homolog comes from the gamete of each parent. After fertilization, both homologs are present in the zygote. In meiosis, the diploid set of chromosomes, present in each cell as homologous pairs, is reduced to a haploid set which contains only a single homolog of a pair. Meiosis thus balances the effects of fertilization, ensuring that the number of chromosomes remains constant from generation to generation. And, as we shall see, meiosis is also a source of new combinations of genetic information within the choromosomes themselves. Meiosis occurs at different times during the life cycles of different organisms. We will not deal with the protists, fungi or plants here and will only discuss meiosis in animals. In contrast to mitosis, meiosis consists of two successive nuclear divisions to produce four daughter nuclei. Each of these daughter nuclei contain half the number of chromosomes present in the original nucleus. Moreover, each daughter nucleus receives just one member of each pair of homologous chromosomes. The big event of DNA replication occurs during interphase, prior to the first meiotic event, meiotic prophase I. Each chromosome consists of two chromatids held together at a centromere. Early in prophase, the homologous chromosomes come together in pairs. Since each chromosome is made up of two identical chromatids, the pairing of homologous chromosomes actually involves four chromatids. Each complex of paired homologous chromosomes is thus known as a tetrad. At this point a crucial process occurs that can alter the genetic makeup of the chromosomes. The process is known as crossing-over, and involves the exchange of segments of one chromosome with corresponding segments from its homologous chromosome. A diagram of this important process is provided for you. Crossing-over is an important mechanism for re-combining the genetic material from two parents--a little bit of nature's genetic engineering. During prophase I, the condensed, replicated chromosomes become visible under a light microscope. The spindle microtubules assemble and the nucleolus disappears. The nuclear envelope begins to break down and most importantly, the pairing of homologous chromosomes and crossing-over occurs. A diagram is provided for you. In Metaphase I, the homologous pairs line up along the equatorial plane of the spindle, which is quite different from mitosis. Spindle fibers associate with the kinetochores of the chromosomes. A diagram is provided for you. During Anaphase I, the homologs, each consisting of two sister chromatids, separate towards their respective spindle poles. A diagram is provided for you. By Telophase I, the homologs have moved to the poles and each chromosome group now contains only half the number of chromosomes as the original nucleus. Moreover, these chromosomes may be different because of crossing-over exchanges. Depending on the species, nuclear envelopes may or may not appear. But meiosis does not end here-- During prophase II, the chromosomes, if at all dispersed, condense again; the nuclear envelope if present, disintegrates again; new spindle fibers begin to form. Each chromosome is still in the form of two chromatids. In Metaphase II, the chromosomes line up at the equatorial plane of the spindle. Each consists of two chromatids. A diagram is provided for you. During Anaphase II, the chromatids of each chromosome separate and each individual chromatid, now called a chromosome, moves toward its respective spindle pole. A diagram is provided for you. Then, at Telophase II, the nuclear envelope reforms, the spindle apparatus disappears and there are now four nuclei in all, each containing the haploid number of chromosomes. A diagram is provided for you. Cytokinesis proceeds as it does following mitosis. Mistakes in meiosis do occur. As you now know, humans have a chromosome number of 46; the haploid number is 23. In all of the homologous pairs except one, the chromosomes appear to be identical in both males and females; these chromosomes are known as autosomes. The structure of one pair, however, differs between male and female; the chromosomes of this pair are know as sex chromosomes. In females, the two sex chromosomes are identical; in males they are dissimilar. One of the male sex chromosomes is the same as the female sex chromosomes; the other is much smaller. The chromosome that is the same in the cells of both males and females is known as the X chromosome. The dissimilar chromosome characteristic of the cells of males is known as the Y chromosome. A number of genetic disorders are caused by abnormalities in the number or structure of either the autosomes or the sex chromosomes. These abnormalities generally result from "mistakes" during meiosis. For example, from time to time, homologous chromosomes fail to separate during the first division of meiosis. Similarly, sometimes chromatids fail to separate during the second division of meiosis. This phenomenon is known as nondisjunction. When nondisjunction occurs in meiosis, the result is gametes with too many or too few chromosomes. A gamete with too few chromosomes, unless the missing chromosome is a sex chromosome, cannot produce a viable embryo. These are spontaneously aborted. A gamete with too many chromosomes sometimes does produce a viable embryo which results in an individual with one extra chromosome in each of their cells. In the vast majority of cases, such fetuses are spontaneously aborted early in pregnancy. Individuals with additional autosomes always have widespread abnormalities. With the exception of those with Down Syndrome, those who are not stillborn typically survive only a few months. Among the few who survive, most are mentally retarded and those who survive are are usually sterile. They frequently have heart and other organ abnormalities as well. One of the most familiar conditions resulting from an abnormality in the number of autosomal chromosomes is Down Syndrome, named after the physician who first described it. It usually involves more than one defect, hence the reference to its being a syndrome. Down syndrome includes, a short, stocky body with a thick neck; mental retardation ranging from mild to severe in different individuals; a large tongue which results in speech defects and often, abnormalities of the heart and other organs. Down syndrome arises when an individual has three, rather than two, copies of chromosome 21. In about 95 percent of the cases, the cause of the abnormality is nondisjunction during formation of a parental gamete, resulting in 47 chromosomes, with an extra copy of chromosome 21 in the cells of the infected individual. It has been known for a number of years that Down syndrome and a number of other disorders involving nondisjunction are more likely to occur among infants born to older women. The reason(s) for this are not known. In about 5 percent of the cases of Down syndrome due to nondisjunction, the extra chromosome comes from the father rather than the mother. Meiosis builds genetic variability in a species. That is, meiosis increases the variety in characteristics among individuals that make up a species' population. A greater range of characteristics in a population improves the chances that some individuals will survive environmental changes and that the species will then continue. Meiosis is also important for the formation of new species and together with the appearance of new genetic characteristics by mutation, meiosis is one of the underlying mechanisms that ensures genetic change in a population over time. 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 cell divides, the result is two cancer cells. Cancer facts:
You may take a quiz on the material in this module. No record of the quiz is made. You decide after the quiz if you really know this material. Return to the Syllabus Page. |
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