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Chapter 12 The Cell Cycle Power. Point® Lecture Presentations for Biology Eighth Edition Neil Chapter 12 The Cell Cycle Power. Point® Lecture Presentations for Biology Eighth Edition Neil Campbell and Jane Reece Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Overview: The Key Roles of Cell Division • The ability of organisms to reproduce Overview: The Key Roles of Cell Division • The ability of organisms to reproduce best distinguishes living things from nonliving matter • The continuity of life is based on the reproduction of cells, or cell division Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -1 Fig. 12 -1

 • In unicellular organisms, division of one cell reproduces the entire organism • • In unicellular organisms, division of one cell reproduces the entire organism • Multicellular organisms depend on cell division for: – Development from a fertilized cell – Growth – Repair • Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -2 100 µm (a) Reproduction 20 µm 200 µm (b) Growth and Fig. 12 -2 100 µm (a) Reproduction 20 µm 200 µm (b) Growth and development (c) Tissue renewal

Fig. 12 -2 a 100 µm (a) Reproduction Fig. 12 -2 a 100 µm (a) Reproduction

Fig. 12 -2 b 200 µm (b) Growth and development Fig. 12 -2 b 200 µm (b) Growth and development

Fig. 12 -2 c 20 µm (c) Tissue renewal Fig. 12 -2 c 20 µm (c) Tissue renewal

Concept 12. 1: Cell division results in genetically identical daughter cells • Most cell Concept 12. 1: Cell division results in genetically identical daughter cells • Most cell division results in daughter cells with identical genetic information, DNA • A special type of division produces nonidentical daughter cells (gametes, or sperm and egg cells) Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Cellular Organization of the Genetic Material • All the DNA in a cell constitutes Cellular Organization of the Genetic Material • All the DNA in a cell constitutes the cell’s genome • A genome can consist of a single DNA molecule (common in prokaryotic cells) or a number of DNA molecules (common in eukaryotic cells) • DNA molecules in a cell are packaged into chromosomes Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -3 20 µm Fig. 12 -3 20 µm

 • Every eukaryotic species has a characteristic number of chromosomes in each cell • Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus • Somatic cells (nonreproductive cells) have two sets of chromosomes • Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells • Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Distribution of Chromosomes During Eukaryotic Cell Division • In preparation for cell division, DNA Distribution of Chromosomes During Eukaryotic Cell Division • In preparation for cell division, DNA is replicated and the chromosomes condense • Each duplicated chromosome has two sister chromatids, which separate during cell division • The centromere is the narrow “waist” of the duplicated chromosome, where the two chromatids are most closely attached Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -4 0. 5 µm Chromosomes Chromosome arm Centromere DNA molecules Chromosome duplication Fig. 12 -4 0. 5 µm Chromosomes Chromosome arm Centromere DNA molecules Chromosome duplication (including DNA synthesis) Sister chromatids Separation of sister chromatids Centromere Sister chromatids

 • Eukaryotic cell division consists of: – Mitosis, the division of the nucleus • Eukaryotic cell division consists of: – Mitosis, the division of the nucleus – Cytokinesis, the division of the cytoplasm • Gametes are produced by a variation of cell division called meiosis • Meiosis yields nonidentical daughter cells that have only one set of chromosomes, half as many as the parent cell Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Concept 12. 2: The mitotic phase alternates with interphase in the cell cycle • Concept 12. 2: The mitotic phase alternates with interphase in the cell cycle • In 1882, the German anatomist Walther Flemming developed dyes to observe chromosomes during mitosis and cytokinesis Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Phases of the Cell Cycle • The cell cycle consists of – Mitotic (M) Phases of the Cell Cycle • The cell cycle consists of – Mitotic (M) phase (mitosis and cytokinesis) – Interphase (cell growth and copying of chromosomes in preparation for cell division) Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

 • Interphase (about 90% of the cell cycle) can be divided into subphases: • Interphase (about 90% of the cell cycle) can be divided into subphases: – G 1 phase (“first gap”) – S phase (“synthesis”) – G 2 phase (“second gap”) • The cell grows during all three phases, but chromosomes are duplicated only during the S phase Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -5 S (DNA synthesis) G 1 s si e in M MIT Fig. 12 -5 S (DNA synthesis) G 1 s si e in M MIT (M) OTIC PHA SE ito Cy si s ok t G 2

 • Mitosis is conventionally divided into five phases: – Prophase – Prometaphase – • Mitosis is conventionally divided into five phases: – Prophase – Prometaphase – Metaphase – Anaphase – Telophase • Cytokinesis is well underway by late telophase Bio. Flix: Mitosis Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -6 G 2 of Interphase Centrosomes Chromatin (with centriole (duplicated) pairs) Prophase Fig. 12 -6 G 2 of Interphase Centrosomes Chromatin (with centriole (duplicated) pairs) Prophase Early mitotic Aster Centromere spindle Nucleolus Nuclear Plasma envelope membrane Chromosome, consisting of two sister chromatids Metaphase Prometaphase Fragments Nonkinetochore of nuclear microtubules envelope Kinetochore microtubule Anaphase Cleavage furrow Metaphase plate Spindle Centrosome at one spindle pole Telophase and Cytokinesis Daughter chromosomes Nuclear envelope forming Nucleolus forming

Fig. 12 -6 a G 2 of Interphase Prometaphase Fig. 12 -6 a G 2 of Interphase Prometaphase

Fig. 12 -6 b G 2 of Interphase Chromatin Centrosomes (with centriole (duplicated) pairs) Fig. 12 -6 b G 2 of Interphase Chromatin Centrosomes (with centriole (duplicated) pairs) Prophase Early mitotic Aster spindle Nucleolus Nuclear Plasma envelope membrane Prometaphase Centromere Chromosome, consisting of two sister chromatids Fragments of nuclear envelope Kinetochore Nonkinetochore microtubules Kinetochore microtubule

Fig. 12 -6 c Metaphase Anaphase Telophase and Cytokinesis Fig. 12 -6 c Metaphase Anaphase Telophase and Cytokinesis

Fig. 12 -6 d Metaphase Anaphase Metaphase plate Spindle Centrosome at one spindle pole Fig. 12 -6 d Metaphase Anaphase Metaphase plate Spindle Centrosome at one spindle pole Telophase and Cytokinesis Cleavage furrow Daughter chromosomes Nuclear envelope forming Nucleolus forming

The Mitotic Spindle: A Closer Look • The mitotic spindle is an apparatus of The Mitotic Spindle: A Closer Look • The mitotic spindle is an apparatus of microtubules that controls chromosome movement during mitosis • During prophase, assembly of spindle microtubules begins in the centrosome, the microtubule organizing center • The centrosome replicates, forming two centrosomes that migrate to opposite ends of the cell, as spindle microtubules grow out from them Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

 • An aster (a radial array of short microtubules) extends from each centrosome • An aster (a radial array of short microtubules) extends from each centrosome • The spindle includes the centrosomes, the spindle microtubules, and the asters Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

 • During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes and • During prometaphase, some spindle microtubules attach to the kinetochores of chromosomes and begin to move the chromosomes • At metaphase, the chromosomes are all lined up at the metaphase plate, the midway point between the spindle’s two poles Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -7 Aster Centrosome Sister chromatids Microtubules Chromosomes Metaphase plate Kinetochores Centrosome 1 Fig. 12 -7 Aster Centrosome Sister chromatids Microtubules Chromosomes Metaphase plate Kinetochores Centrosome 1 µm Overlapping nonkinetochore microtubules Kinetochore microtubules 0. 5 µm

 • In anaphase, sister chromatids separate and move along the kinetochore microtubules toward • In anaphase, sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell • The microtubules shorten by depolymerizing at their kinetochore ends Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -8 EXPERIMENT Kinetochore Spindle pole Mark RESULTS CONCLUSION Chromosome movement Motor Microtubule Fig. 12 -8 EXPERIMENT Kinetochore Spindle pole Mark RESULTS CONCLUSION Chromosome movement Motor Microtubule protein Chromosome Kinetochore Tubulin subunits

Fig. 12 -8 a EXPERIMENT Kinetochore Spindle pole Mark RESULTS Fig. 12 -8 a EXPERIMENT Kinetochore Spindle pole Mark RESULTS

Fig. 12 -8 b CONCLUSION Chromosome movement Microtubule Motor protein Chromosome Kinetochore Tubulin Subunits Fig. 12 -8 b CONCLUSION Chromosome movement Microtubule Motor protein Chromosome Kinetochore Tubulin Subunits

 • Nonkinetochore microtubules from opposite poles overlap and push against each other, elongating • Nonkinetochore microtubules from opposite poles overlap and push against each other, elongating the cell • In telophase, genetically identical daughter nuclei form at opposite ends of the cell Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Cytokinesis: A Closer Look • In animal cells, cytokinesis occurs by a process known Cytokinesis: A Closer Look • In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow • In plant cells, a cell plate forms during cytokinesis Animation: Cytokinesis Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Video: Animal Mitosis Video: Sea Urchin (Time Lapse) Copyright © 2008 Pearson Education, Inc. Video: Animal Mitosis Video: Sea Urchin (Time Lapse) Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -9 100 µm Cleavage furrow Contractile ring of microfilaments Vesicles forming cell Fig. 12 -9 100 µm Cleavage furrow Contractile ring of microfilaments Vesicles forming cell plate Wall of parent cell Cell plate 1 µm New cell wall Daughter cells (a) Cleavage of an animal cell (SEM) Daughter cells (b) Cell plate formation in a plant cell (TEM)

Fig. 12 -9 a 100 µm Cleavage furrow Contractile ring of microfilaments Daughter cells Fig. 12 -9 a 100 µm Cleavage furrow Contractile ring of microfilaments Daughter cells (a) Cleavage of an animal cell (SEM)

Fig. 12 -9 b Vesicles forming cell plate Wall of parent cell Cell plate Fig. 12 -9 b Vesicles forming cell plate Wall of parent cell Cell plate 1 µm New cell wall Daughter cells (b) Cell plate formation in a plant cell (TEM)

Fig. 12 -10 Nucleus Nucleolus 1 Prophase Chromatin condensing Chromosomes 2 Prometaphase 3 Metaphase Fig. 12 -10 Nucleus Nucleolus 1 Prophase Chromatin condensing Chromosomes 2 Prometaphase 3 Metaphase Cell plate 4 Anaphase 5 Telophase 10 µm

Fig. 12 -10 a Nucleus Nucleolus 1 Prophase Chromatin condensing Fig. 12 -10 a Nucleus Nucleolus 1 Prophase Chromatin condensing

Fig. 12 -10 b Chromosomes 2 Prometaphase Fig. 12 -10 b Chromosomes 2 Prometaphase

Fig. 12 -10 c 3 Metaphase Fig. 12 -10 c 3 Metaphase

Fig. 12 -10 d 4 Anaphase Fig. 12 -10 d 4 Anaphase

Fig. 12 -10 e Cell plate 5 Telophase 10 µm Fig. 12 -10 e Cell plate 5 Telophase 10 µm

Binary Fission • Prokaryotes (bacteria and archaea) reproduce by a type of cell division Binary Fission • Prokaryotes (bacteria and archaea) reproduce by a type of cell division called binary fission • In binary fission, the chromosome replicates (beginning at the origin of replication), and the two daughter chromosomes actively move apart Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -11 -1 Origin of replication E. coli cell Two copies of origin Fig. 12 -11 -1 Origin of replication E. coli cell Two copies of origin Cell wall Plasma membrane Bacterial chromosome

Fig. 12 -11 -2 Origin of replication E. coli cell Two copies of origin Fig. 12 -11 -2 Origin of replication E. coli cell Two copies of origin Origin Cell wall Plasma membrane Bacterial chromosome Origin

Fig. 12 -11 -3 Origin of replication E. coli cell Two copies of origin Fig. 12 -11 -3 Origin of replication E. coli cell Two copies of origin Origin Cell wall Plasma membrane Bacterial chromosome Origin

Fig. 12 -11 -4 Origin of replication E. coli cell Two copies of origin Fig. 12 -11 -4 Origin of replication E. coli cell Two copies of origin Origin Cell wall Plasma membrane Bacterial chromosome Origin

The Evolution of Mitosis • Since prokaryotes evolved before eukaryotes, mitosis probably evolved from The Evolution of Mitosis • Since prokaryotes evolved before eukaryotes, mitosis probably evolved from binary fission • Certain protists exhibit types of cell division that seem intermediate between binary fission and mitosis Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -12 Bacterial chromosome (a) Bacteria Chromosomes Microtubules (b) Dinoflagellates Intact nuclear envelope Fig. 12 -12 Bacterial chromosome (a) Bacteria Chromosomes Microtubules (b) Dinoflagellates Intact nuclear envelope Kinetochore microtubule Intact nuclear envelope (c) Diatoms and yeasts Kinetochore microtubule Fragments of nuclear envelope (d) Most eukaryotes

Fig. 12 -12 ab Bacterial chromosome (a) Bacteria Chromosomes Microtubules (b) Dinoflagellates Intact nuclear Fig. 12 -12 ab Bacterial chromosome (a) Bacteria Chromosomes Microtubules (b) Dinoflagellates Intact nuclear envelope

Fig. 12 -12 cd Kinetochore microtubule Intact nuclear envelope (c) Diatoms and yeasts Kinetochore Fig. 12 -12 cd Kinetochore microtubule Intact nuclear envelope (c) Diatoms and yeasts Kinetochore microtubule (d) Most eukaryotes Fragments of nuclear envelope

Concept 12. 3: The eukaryotic cell cycle is regulated by a molecular control system Concept 12. 3: The eukaryotic cell cycle is regulated by a molecular control system • The frequency of cell division varies with the type of cell • These cell cycle differences result from regulation at the molecular level Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Evidence for Cytoplasmic Signals • The cell cycle appears to be driven by specific Evidence for Cytoplasmic Signals • The cell cycle appears to be driven by specific chemical signals present in the cytoplasm • Some evidence for this hypothesis comes from experiments in which cultured mammalian cells at different phases of the cell cycle were fused to form a single cell with two nuclei Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -13 EXPERIMENT Experiment 1 S G 1 Experiment 2 M G 1 Fig. 12 -13 EXPERIMENT Experiment 1 S G 1 Experiment 2 M G 1 RESULTS S S When a cell in the S phase was fused with a cell in G 1, the G 1 nucleus immediately entered the S phase—DNA was synthesized. M M When a cell in the M phase was fused with a cell in G 1, the G 1 nucleus immediately began mitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated.

The Cell Cycle Control System • The sequential events of the cell cycle are The Cell Cycle Control System • The sequential events of the cell cycle are directed by a distinct cell cycle control system, which is similar to a clock • The cell cycle control system is regulated by both internal and external controls • The clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -14 G 1 checkpoint Control system G 1 M G 2 M Fig. 12 -14 G 1 checkpoint Control system G 1 M G 2 M checkpoint G 2 checkpoint S

 • For many cells, the G 1 checkpoint seems to be the most • For many cells, the G 1 checkpoint seems to be the most important one • If a cell receives a go-ahead signal at the G 1 checkpoint, it will usually complete the S, G 2, and M phases and divide • If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G 0 phase Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -15 G 0 G 1 checkpoint G 1 (a) Cell receives a Fig. 12 -15 G 0 G 1 checkpoint G 1 (a) Cell receives a go-ahead signal G 1 (b) Cell does not receive a go-ahead signal

The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases • Two types of regulatory proteins The Cell Cycle Clock: Cyclins and Cyclin-Dependent Kinases • Two types of regulatory proteins are involved in cell cycle control: cyclins and cyclindependent kinases (Cdks) • The activity of cyclins and Cdks fluctuates during the cell cycle • MPF (maturation-promoting factor) is a cyclin. Cdk complex that triggers a cell’s passage past the G 2 checkpoint into the M phase Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -16 5 30 4 20 3 2 10 1 0 100 200 Fig. 12 -16 5 30 4 20 3 2 10 1 0 100 200 300 Time (min) 400 0 500 % of dividing cells (– ) Protein kinase activity (– ) RESULTS

Fig. 12 -17 M S G 1 M G 2 G 1 S G Fig. 12 -17 M S G 1 M G 2 G 1 S G 2 M G 1 MPF activity Cyclin concentration Time (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle 1 G Cdk Degraded cyclin M G 2 checkpoint Cyclin is degraded MPF Cdk Cyclin (b) Molecular mechanisms that help regulate the cell cycle Cyclin accumulation S

Fig. 12 -17 a M G 1 S G 2 M G 1 MPF Fig. 12 -17 a M G 1 S G 2 M G 1 MPF activity Cyclin concentration Time (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle

Fig. 12 -17 b 1 G Degraded cyclin M G 2 Cdk checkpoint Cyclin Fig. 12 -17 b 1 G Degraded cyclin M G 2 Cdk checkpoint Cyclin is degraded MPF Cyclin (b) Molecular mechanisms that help regulate the cell cycle Cyclin accumulation S Cdk

Stop and Go Signs: Internal and External Signals at the Checkpoints • An example Stop and Go Signs: Internal and External Signals at the Checkpoints • An example of an internal signal is that kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase • Some external signals are growth factors, proteins released by certain cells that stimulate other cells to divide • For example, platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells in culture Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -18 Scalpels Petri plate Without PDGF cells fail to divide With PDGF Fig. 12 -18 Scalpels Petri plate Without PDGF cells fail to divide With PDGF cells proliferate Cultured fibroblasts 10 µm

 • Another example of external signals is densitydependent inhibition, in which crowded cells • Another example of external signals is densitydependent inhibition, in which crowded cells stop dividing • Most animal cells also exhibit anchorage dependence, in which they must be attached to a substratum in order to divide Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -19 Anchorage dependence Density-dependent inhibition 25 µm (a) Normal mammalian cells (b) Fig. 12 -19 Anchorage dependence Density-dependent inhibition 25 µm (a) Normal mammalian cells (b) Cancer cells

 • Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence Copyright © 2008 • Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Loss of Cell Cycle Controls in Cancer Cells • Cancer cells do not respond Loss of Cell Cycle Controls in Cancer Cells • Cancer cells do not respond normally to the body’s control mechanisms • Cancer cells may not need growth factors to grow and divide: – They make their own growth factor – They may convey a growth factor’s signal without the presence of the growth factor – They may have an abnormal cell cycle control system Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

 • A normal cell is converted to a cancerous cell by a process • A normal cell is converted to a cancerous cell by a process called transformation • Cancer cells form tumors, masses of abnormal cells within otherwise normal tissue • If abnormal cells remain at the original site, the lump is called a benign tumor • Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form secondary tumors Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

Fig. 12 -20 Lymph vessel Tumor Blood vessel Cancer cell Metastatic tumor Glandular tissue Fig. 12 -20 Lymph vessel Tumor Blood vessel Cancer cell Metastatic tumor Glandular tissue 1 A tumor grows from a single cancer cell. 2 Cancer cells invade neighboring tissue. 3 Cancer cells spread to other parts of the body. 4 Cancer cells may survive and establish a new tumor in another part of the body.

Fig. 12 -UN 1 G 1 S Cytokinesis Mitosis G 2 MITOTIC (M) PHASE Fig. 12 -UN 1 G 1 S Cytokinesis Mitosis G 2 MITOTIC (M) PHASE Prophase Telophase and Cytokinesis Prometaphase Anaphase Metaphase

Fig. 12 -UN 2 Fig. 12 -UN 2

Fig. 12 -UN 3 Fig. 12 -UN 3

Fig. 12 -UN 4 Fig. 12 -UN 4

Fig. 12 -UN 5 Fig. 12 -UN 5

Fig. 12 -UN 6 Fig. 12 -UN 6

You should now be able to: 1. Describe the structural organization of the prokaryotic You should now be able to: 1. Describe the structural organization of the prokaryotic genome and the eukaryotic genome 2. List the phases of the cell cycle; describe the sequence of events during each phase 3. List the phases of mitosis and describe the events characteristic of each phase 4. Draw or describe the mitotic spindle, including centrosomes, kinetochore microtubules, nonkinetochore microtubules, and asters Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings

5. Compare cytokinesis in animals and plants 6. Describe the process of binary fission 5. Compare cytokinesis in animals and plants 6. Describe the process of binary fission in bacteria and explain how eukaryotic mitosis may have evolved from binary fission 7. Explain how the abnormal cell division of cancerous cells escapes normal cell cycle controls 8. Distinguish between benign, malignant, and metastatic tumors Copyright © 2008 Pearson Education, Inc. , publishing as Pearson Benjamin Cummings