Transcript the lecture in Powerpoint Format

Chapter 11
How Genes Are Controlled
PowerPoint Lectures for
Campbell Biology: Concepts & Connections, Seventh Edition
Reece, Taylor, Simon, and Dickey
© 2012 Pearson Education, Inc.
Lecture by Edward J. Zalisko
Introduction
 Cloning is the creation of an individual by asexual
reproduction.
 The ability to clone an animal from a single cell
demonstrates that every adult body cell
– contains a complete genome that is
– capable of directing the production of all the cell types
in an organism.
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Introduction
 Cloning has been attempted to save endangered
species.
 However, cloning
– does not increase genetic diversity and
– may trivialize the tragedy of extinction and detract from
efforts to preserve natural habitats.
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Figure 11.0_1
Chapter 11: Big Ideas
Control of Gene
Expression
The Genetic Basis
of Cancer
Cloning of Plants
and Animals
CONTROL OF GENE
EXPRESSION
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11.1 Proteins interacting with DNA turn
prokaryotic genes on or off in response to
environmental changes
 Gene regulation is the turning on and off of genes.
 Gene expression is the overall process of
information flow from genes to proteins.
 The control of gene expression allows cells to
produce specific kinds of proteins when and where
they are needed.
 Our earlier understanding of gene control came from
the study of E. coli.
© 2012 Pearson Education, Inc.
Figure 11.1A
E. coli
11.1 Proteins interacting with DNA turn
prokaryotic genes on or off in response to
environmental changes
 A cluster of genes with related functions, along with
the control sequences, is called an operon.
 With few exceptions, operons only exist in
prokaryotes.
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11.1 Proteins interacting with DNA turn
prokaryotic genes on or off in response to
environmental changes
 When an E. coli encounters lactose, all the enzymes
needed for its metabolism are made at once using
the lactose operon.
 The lactose (lac) operon includes
1. three adjacent lactose-utilization genes,
2. a promoter sequence where RNA polymerase binds and
initiates transcription of all three lactose genes, and
3. an operator sequence where a repressor can bind and
block RNA polymerase action.
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11.1 Proteins interacting with DNA turn
prokaryotic genes on or off in response to
environmental changes
 Regulation of the lac operon
– A regulatory gene, located outside the operon, codes
for a repressor protein.
– In the absence of lactose, the repressor binds to the
operator and prevents RNA polymerase action.
– Lactose inactivates the repressor, so
– the operator is unblocked,
– RNA polymerase can bind to the promoter, and
– all three genes of the operon are transcribed.
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Figure 11.1B
Operon turned off (lactose is absent):
OPERON
Regulatory
gene
Promoter Operator
Lactose-utilization genes
DNA
RNA polymerase cannot
attach to the promoter
mRNA
Protein
Active
repressor
Operon turned on (lactose inactivates the repressor):
DNA
RNA polymerase is
bound to the promoter
mRNA
Translation
Protein
Lactose
Inactive
repressor
Enzymes for lactose utilization
11.1 Proteins interacting with DNA turn
prokaryotic genes on or off in response to
environmental changes
 There are two types of repressor-controlled operons.
– In the lac operon, the repressor is
– active when alone and
– inactive when bound to lactose.
– In the trp bacterial operon, the repressor is
– inactive when alone and
– active when bound to the amino acid tryptophan (Trp).
© 2012 Pearson Education, Inc.
Figure 11.1C
trp operon
lac operon
Promoter Operator Gene
DNA
Active
repressor
Active
repressor
Inactive
repressor
Lactose
Inactive
repressor
Tryptophan
11.1 Proteins interacting with DNA turn
prokaryotic genes on or off in response to
environmental changes
 Another type of operon control involves activators,
proteins that turn operons on by
– binding to DNA and
– making it easier for RNA polymerase to bind to the
promoter.
 Activators help control a wide variety of operons.
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11.2 Chromosome structure and chemical
modifications can affect gene expression
 Differentiation
– involves cell specialization, in structure and function, and
– is controlled by turning specific sets of genes on or off.
 Almost all of the cells in an organism contain an
identical genome.
 The differences between cell types are
– not due to the presence of different genes but instead
– due to selective gene expression.
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11.2 Chromosome structure and chemical
modifications can affect gene expression
 Eukaryotic chromosomes undergo multiple levels of
folding and coiling, called DNA packing.
– Nucleosomes are formed when DNA is wrapped around
histone proteins.
– This packaging gives a “beads on a string” appearance.
– Each nucleosome bead includes DNA plus eight histones.
– Stretches of DNA, called linkers, join consecutive nucleosomes.
– At the next level of packing, the beaded string is wrapped
into a tight helical fiber.
– This fiber coils further into a thick supercoil.
– Looping and folding can further compact the DNA.
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11.2 Chromosome structure and chemical
modifications can affect gene expression
 DNA packing can prevent gene expression by
preventing RNA polymerase and other
transcription proteins from contacting the DNA.
 Cells seem to use higher levels of packing for
long-term inactivation of genes.
 Highly compacted chromatin, found in varying
regions of interphase chromosomes, is
generally not expressed at all.
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11.2 Chromosome structure and chemical
modifications can affect gene expression
 Chemical modification of DNA bases or histone
proteins can result in epigenetic inheritance.
– Certain enzymes can add a methyl group to DNA bases,
without changing the sequence of the bases.
– Individual genes are usually more methylated in cells in
which the genes are not expressed. Once methylated,
genes usually stay that way through successive cell
divisions in an individual.
© 2012 Pearson Education, Inc.
11.2 Chromosome structure and chemical
modifications can affect gene expression
– Removal of the extra methyl groups can turn on some of
these genes.
– Inheritance of traits transmitted by mechanisms not
directly involving the nucleotide sequence is called
epigenetic inheritance. These modifications can be
reversed by processes not yet fully understood.
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11.2 Chromosome structure and chemical
modifications can affect gene expression
 X-chromosome inactivation
– In female mammals, one of the two X chromosomes is
highly compacted and transcriptionally inactive.
– Either the maternal or paternal chromosome is randomly
inactivated.
– Inactivation occurs early in embryonic development, and all
cellular descendants have the same inactivated
chromosome.
– An inactivated X chromosome is called a Barr body.
– Tortoiseshell fur coloration is due to inactivation of X
chromosomes in heterozygous female cats.
© 2012 Pearson Education, Inc.
Figure 11.2A
DNA double helix
(2-nm diameter)
Metaphase
chromosome
Nucleosome
(10-nm diameter)
Linker
“Beads on
a string”
Histones Supercoil
(300-nm diameter)
Tight helical
fiber (30-nm
diameter)
700 nm
Figure 11.2B
Early Embryo
Adult
Two cell populations
X chromosomes
Allele for
orange fur
Cell division
and random
X chromosome Active X
inactivation Inactive X
Allele for
black fur
Inactive X
Active X
Orange
fur
Black fur
Figure 11.2B_1
Early Embryo
Adult
Two cell populations
X chromosomes
Allele for
orange fur
Cell division
and random
X chromosome Active X
inactivation Inactive X
Allele for
black fur
Inactive X
Active X
Orange
fur
Black fur
11.3 Complex assemblies of proteins control
eukaryotic transcription
 Prokaryotes and eukaryotes employ regulatory
proteins (activators and repressors) that
– bind to specific segments of DNA and
– either promote or block the binding of RNA polymerase,
turning the transcription of genes on and off.
 In eukaryotes, activator proteins seem to be more
important than repressors. Thus, the default state for
most genes seems to be off.
 A typical plant or animal cell needs to turn on and
transcribe only a small percentage of its genes.
© 2012 Pearson Education, Inc.
11.3 Complex assemblies of proteins control
eukaryotic transcription
 Eukaryotic RNA polymerase requires the assistance
of proteins called transcription factors.
Transcription factors include
– activator proteins, which bind to DNA sequences called
enhancers and initiate gene transcription. The binding of
the activators leads to bending of the DNA.
– Other transcription factor proteins interact with the bound
activators, which then collectively bind as a complex at
the gene’s promoter.
 RNA polymerase then attaches to the promoter and
transcription begins.
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Figure 11.3
Enhancers
Promoter
Gene
DNA
Activator
proteins
Transcription
factors
Other
proteins
RNA polymerase
Bending
of DNA
Transcription
11.3 Complex assemblies of proteins control
eukaryotic transcription
 Silencers are repressor proteins that
– may bind to DNA sequences and
– inhibit transcription.
 Coordinated gene expression in eukaryotes often
depends on the association of a specific
combination of control elements with every gene
of a particular metabolic pathway.
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11.4 Eukaryotic RNA may be spliced in more
than one way
 Alternative RNA splicing
– produces different mRNAs from the same transcript,
– results in the production of more than one polypeptide
from the same gene, and
– may be common in humans.
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Figure 11.4
Exons
1
DNA
2
4
3
Introns
Cap
RNA
1
transcript
5
Introns
Tail
2
5
4
3
RNA splicing
or
mRNA
1
2 3
5
1
2 4
5
11.5 Small RNAs play multiple roles in
controlling gene expression
 Only about 1.5% of the human genome codes for
proteins. (This is also true of many other multicellular
eukaryotes.)
 Another small fraction of DNA consists of genes for
ribosomal RNA and transfer RNA.
 A flood of recent data suggests that a significant
amount of the remaining genome is transcribed into
functioning but non-protein-coding RNAs, including a
variety of small RNAs.
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11.5 Small RNAs play multiple roles in
controlling gene expression
 microRNAs (miRNAs) can bind to complementary
sequences on mRNA molecules either
– degrading the target mRNA or
– blocking its translation.
 RNA interference (RNAi) is the use of miRNA to
artificially control gene expression by injecting
miRNAs into a cell to turn off a specific gene
sequence.
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Figure 11.5
Protein
miRNA
1
miRNAprotein
complex
2
Target mRNA
3
or
4
Translation
blocked
mRNA degraded
11.6 Later stages of gene expression are also
subject to regulation
 After mRNA is fully processed and transported to
the cytoplasm, gene expression can still be
regulated by
– breakdown of mRNA,
– initiation of translation,
– protein activation, and
– protein breakdown.
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Figure 11.6
Folding of the polypeptide
and the formation of
S—S linkages
Cleavage
S S
Initial polypeptide
(inactive)
Folded polypeptide
(inactive)
S S
Active form
of insulin
11.7 Review: Multiple mechanisms regulate gene
expression in eukaryotes
 Multiple control points exist where gene
expression in eukaryotes can be
– turned on or off or
– speeded up, or slowed down.
 These control points are like a series of pipes
carrying water from your local water supply to a
faucet in your home. Valves in this series of pipes
are like the control points in gene expression.
Animation: Protein Degradation
Animation: Protein Processing
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Figure 11.7_1
Chromosome
Chromosome
DNA unpacking
Other changes to the DNA
DNA
Gene
Gene
Transcription
Exon
RNA transcript
Intron
Addition of a cap and tail
Splicing
Tail
Cap
mRNA in nucleus
Flow through
NUCLEUS nuclear envelope
CYTOPLASM
Figure 11.7_2
mRNA in cytoplasm
CYTOPLASM
Breakdown of mRNA
Brokendown
mRNA
Translation
Polypeptide
Polypeptide
Cleavage, modification,
activation
Active
protein
Active protein
Breakdown
of protein
Amino
acids
11.7 Review: Multiple mechanisms regulate gene
expression in eukaryotes
 These controls points include:
1. chromosome changes and DNA unpacking,
2. control of transcription,
3. control of RNA processing including the
– addition of a cap and tail and
– splicing,
4. flow through the nuclear envelope,
5. breakdown of mRNA,
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11.7 Review: Multiple mechanisms regulate gene
expression in eukaryotes
6. control of translation, and
7. control after translation including
– cleavage/modification/activation of proteins and
– breakdown of protein.
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11.8 Cell signaling and cascades of gene
expression direct animal development
 Early research on gene expression and embryonic
development came from studies of a fruit fly,
revealing the control of these key events.
1. Orientation of the head-to-tail, top-to-bottom, and side-toside axes are determined by early genes in the egg that
produce proteins and maternal mRNAs.
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11.8 Cell signaling and cascades of gene
expression direct animal development
2. Segmentation of the body is influenced by cascades of
proteins that diffuse through the cell layers.
3. Adult features develop under the influence of homeotic
genes, master control genes that determine the anatomy
of the parts of the body.
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Figure 11.8A
Eye
Antenna
Extra pair
of legs
Figure 11.8B
Egg cell within ovarian follicle
Egg cell
1
Follicle cells
2
Egg cell and follicle
cells signaling
each other
Gene expression
Growth of egg cell
Localization of “head” mRNA
Egg cell
“Head”
mRNA
Cascades of
gene expression
Fertilization and mitosis
Embryo
Body segments
3
Expression of homeotic genes
and cascades of gene expression
Adult fly
4
11.9 CONNECTION: DNA microarrays test for
the transcription of many genes at once
 DNA microarrays help researchers study the
expression of large groups of genes.
 A DNA microarray
– contains DNA sequences arranged on a grid and
– is used to test for transcription in the following way:
– mRNA from a specific cell type is isolated,
– fluorescent cDNA is produced from the mRNA,
– cDNA is applied to the microarray,
– unbound cDNA is washed off, and
– complementary cDNA is detected by fluorescence.
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Figure 11.9
DNA microarray
Each well contains DNA
from a particular gene.
Actual size
(6,400 genes)
1 mRNA
is isolated.
4 Unbound
Reverse transcriptase
and fluorescent DNA
nucleotides
cDNA is rinsed
away.
3
2
cDNA is made
from mRNA.
Fluorescent
spot
cDNA is applied
to the wells.
Nonfluorescent
spot
cDNA
DNA of an
expressed gene
DNA of an
unexpressed gene
11.9 CONNECTION: DNA microarrays test for
the transcription of many genes at once
 DNA microarrays are a potential boon to medical
research.
– In 2002, a study showed that DNA microarray data can
classify different types of leukemia, helping to identify
which chemotherapies will be most effective.
– Other research suggests that many cancers have a
variety of subtypes with different gene expression
patterns.
– DNA microarrays also reveal general profiles of gene
expression over the lifetime of an organism.
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11.10 Signal transduction pathways convert
messages received at the cell surface to
responses within the cell
 A signal transduction pathway is a series of
molecular changes that convert a signal on the
target cell’s surface to a specific response within
the cell.
 Signal transduction pathways are crucial to many
cellular functions.
Animation: Overview of Cell Signaling
Animation: Signal Transduction Pathways
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Figure 11.10
Signaling cell
EXTRACELLULAR FLUID
Signaling
molecule
1
Receptor
protein
2
Target cell
Plasma
membrane
3
Relay
proteins
Signal
transduction
pathway
Transcription factor
(activated)
4
NUCLEUS
DNA
5
mRNA
Transcription
6
CYTOPLASM
New
protein
Translation
Figure 11.10_1
Signaling cell
EXTRACELLULAR FLUID
Signaling
molecule
1
Receptor
protein
2
Target cell
3
Relay
proteins
Signal
transduction
pathway
Plasma
membrane
Figure 11.10_2
Transcription factor
(activated)
4
NUCLEUS
DNA
5
mRNA
Transcription
6
CYTOPLASM
New
protein
Translation
11.11 EVOLUTION CONNECTION: Cellsignaling systems appeared early in the
evolution of life
 In the yeast used to make bread, beer, and wine,
mating is controlled by a signal transduction
pathway.
 These yeast cells identify their mates by
chemical signaling.
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11.11 EVOLUTION CONNECTION: Cellsignaling systems appeared early in the
evolution of life
 Yeast have two mating types: a and .
– Each produces a chemical factor that binds to
receptors on cells of the opposite mating type.
– Binding to receptors triggers growth toward the other
cell and fusion.
 Cell signaling processes in multicellular
organisms are derived from those in unicellular
organisms such as bacteria and yeast.
© 2012 Pearson Education, Inc.
Figure 11.11
Receptor
 factor

a
Yeast cell,
mating type a
a factor

a
a/
Yeast cell,
mating type 
CLONING OF PLANTS
AND ANIMALS
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11.12 Plant cloning shows that differentiated cells
may retain all of their genetic potential
 Most differentiated cells retain a full set of genes,
even though only a subset may be expressed.
Evidence is available from
– plant cloning, in which a root cell can divide to form an
adult plant and
– salamander limb regeneration, in which the cells in
the leg stump dedifferentiate, divide, and then
redifferentiate, giving rise to a new leg.
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Figure 11.12
Root of
carrot plant
Single cell
Root cells cultured
in growth medium
Cell division
in culture
Plantlet
Adult plant
11.13 Nuclear transplantation can be used to
clone animals
 Animal cloning can be achieved using nuclear
transplantation, in which the nucleus of an egg
cell or zygote is replaced with a nucleus from an
adult somatic cell.
 Using nuclear transplantation to produce new
organisms is called reproductive cloning. It was
first used in mammals in 1997 to produce the
sheep Dolly.
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11.13 Nuclear transplantation can be used to
clone animals
 Another way to clone uses embryonic stem (ES)
cells harvested from a blastocyst. This procedure
can be used to produce
– cell cultures for research or
– stem cells for therapeutic treatments.
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Figure 11.13
Donor
cell
Nucleus from
the donor cell
Reproductive
cloning
Blastocyst
The blastocyst is
implanted in a
surrogate mother.
The nucleus is
removed from
an egg cell.
A somatic cell
from an adult donor
is added.
The cell grows in
culture to produce
an early embryo
(blastocyst).
A clone of the
donor is born.
Therapeutic
cloning
Embryonic stem cells
are removed from the
blastocyst and grown
in culture.
The stem cells are
induced to form
specialized cells.
11.14 CONNECTION: Reproductive cloning has
valuable applications, but human
reproductive cloning raises ethical issues
 Since Dolly’s landmark birth in 1997, researchers
have cloned many other mammals, including mice,
cats, horses, cows, mules, pigs, rabbits, ferrets,
and dogs.
 Cloned animals can show differences in anatomy
and behavior due to
– environmental influences and
– random phenomena.
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11.14 CONNECTION: Reproductive cloning has
valuable applications, but human
reproductive cloning raises ethical issues
 Reproductive cloning is used to produce animals
with desirable traits to
– produce better agricultural products,
– produce therapeutic agents, and
– restock populations of endangered animals.
 Human reproductive cloning raises many ethical
concerns.
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11.15 CONNECTION: Therapeutic cloning can
produce stem cells with great medical
potential
 When grown in laboratory culture, stem cells can
– divide indefinitely and
– give rise to many types of differentiated cells.
 Adult stem cells can give rise to many, but not
all, types of cells.
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11.15 CONNECTION: Therapeutic cloning can
produce stem cells with great medical
potential
 Embryonic stem cells are considered more
promising than adult stem cells for medical
applications.
 The ultimate aim of therapeutic cloning is to
supply cells for the repair of damaged or diseased
organs.
© 2012 Pearson Education, Inc.
Figure 11.15
Blood cells
Adult stem
cells in bone
marrow
Nerve cells
Cultured
embryonic
stem cells
Heart muscle cells
Different culture
conditions
Different types of
differentiated cells
THE GENETIC BASIS
OF CANCER
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11.16 Cancer results from mutations in genes
that control cell division
 Mutations in two types of genes can cause cancer.
1. Oncogenes
– Proto-oncogenes are normal genes that promote cell division.
– Mutations to proto-oncogenes create cancer-causing
oncogenes that often stimulate cell division.
2. Tumor-suppressor genes
– Tumor-suppressor genes normally inhibit cell division or
function in the repair of DNA damage.
– Mutations inactivate the genes and allow uncontrolled division
to occur.
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Figure 11.16A
Proto-oncogene
(for a protein that stimulates cell division)
DNA
A mutation within
the gene
Multiple copies
of the gene
Oncogene
Hyperactive
growthstimulating
protein in a
normal amount
The gene is moved to
a new DNA locus,
under new controls
New promoter
Normal growthstimulating
protein
in excess
Normal growthstimulating
protein
in excess
Figure 11.16B
Tumor-suppressor gene
Normal
growthinhibiting
protein
Cell division
under control
Mutated tumor-suppressor gene
Defective,
nonfunctioning
protein
Cell division
not under control
11.17 Multiple genetic changes underlie the
development of cancer
 Usually four or more somatic mutations are
required to produce a full-fledged cancer cell.
 One possible scenario is the stepwise
development of colorectal cancer.
1. An oncogene arises or is activated, resulting in
increased cell division in apparently normal cells in the
colon lining.
2. Additional DNA mutations cause the growth of a small
benign tumor (polyp) in the colon wall.
3. Additional mutations lead to a malignant tumor with the
potential to metastasize.
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Figure 11.17A
An oncogene A tumor-suppressor
DNA
changes: is activated gene is inactivated
A second tumorsuppressor gene
is inactivated
Cellular
Increased
changes: cell division
1
Growth of a
malignant tumor
3
Colon wall
Growth of a polyp
2
Figure 11.17B
1
Chromosomes mutation
Normal
cell
2
mutations
3
4
mutations mutations
Malignant
cell
11.18 Faulty proteins can interfere with normal
signal transduction pathways
 Proto-oncogenes and tumor-suppressor genes often
code for proteins involved in signal transduction
pathways leading to gene expression.
 Two main types of signal transduction pathways
lead to the synthesis of proteins that influence cell
division.
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11.18 Faulty proteins can interfere with normal
signal transduction pathways
1. One pathway produces a product that stimulates
cell division.
– In a healthy cell, the product of the ras protooncogene relays a signal when growth factor binds
to a receptor.
– But in a cancerous condition, the product of the ras
proto-oncogene relays the signal in the absence of a
growth factor, leading to uncontrolled growth.
– Mutations in ras occur in more than 30% of human
cancers.
© 2012 Pearson Education, Inc.
Figure 11.18A
Growth factor
Receptor
Target cell
Hyperactive
relay protein
(product of
ras oncogene)
issues signals
on its own
Normal product
of ras gene
Relay
proteins
Transcription
factor
(activated)
CYTOPLASM
DNA
NUCLEUS
Transcription
Protein that
stimulates
cell division
Translation
11.18 Faulty proteins can interfere with normal
signal transduction pathways
2. A second pathway produces a product that
inhibits cell division.
– The normal product of the p53 gene is a transcription
factor that normally activates genes for factors that
inhibit cell division.
– In the absence of functional p53, cell division
continues because the inhibitory protein is not
produced.
– Mutations in p53 occur in more than 50% of human
cancers.
© 2012 Pearson Education, Inc.
Figure 11.18B
Growth-inhibiting
factor
Receptor
Relay
proteins
Transcription factor
(activated)
Nonfunctional transcription
factor (product of faulty p53
tumor-suppressor gene)
cannot trigger
transcription
Normal product
of p53 gene
Transcription
Protein that
inhibits
cell division
Translation
Protein absent
(cell division
not inhibited)
11.19 CONNECTION: Lifestyle choices can
reduce the risk of cancer
 After heart disease, cancer is the second-leading
cause of death in most industrialized nations.
 Cancer can run in families if an individual inherits an
oncogene or a mutant allele of a tumor-suppressor
gene that makes cancer one step closer.
 But most cancers cannot be associated with an
inherited mutation.
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11.19 CONNECTION: Lifestyle choices can
reduce the risk of cancer
 Carcinogens are cancer-causing agents that alter
DNA.
 Most mutagens (substances that promote
mutations) are carcinogens.
 Two of the most potent carcinogens (mutagens)
are
– X-rays and
– ultraviolet radiation in sunlight.
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11.19 CONNECTION: Lifestyle choices can
reduce the risk of cancer
 The one substance known to cause more cases and
types of cancer than any other single agent is
tobacco.
– More people die of lung cancer than any other form of
cancer.
– Although most tobacco-related cancers come from
smoking, passive inhalation of second-hand smoke is
also a risk.
– Tobacco use, sometimes in combination with alcohol
consumption, causes cancers in addition to lung cancer.
© 2012 Pearson Education, Inc.
11.19 CONNECTION: Lifestyle choices can
reduce the risk of cancer
 Healthy lifestyles that reduce the risks of cancer
include
– avoiding carcinogens, including the sun and tobacco
products,
– exercising adequately,
– regular medical checks for common types of cancer, and
– a healthy high-fiber, low-fat diet including plenty of fruits
and vegetables.
© 2012 Pearson Education, Inc.
Table 11.19