Cell Biology and Cancer by National Institutes of Health. - HTML preview

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nuclear test displayed a significant increase in thyroid cancer).

Carcinogenesis from ionizing radiation is believed to occur through the

formation of mutagenic oxygen free radicals. Ionizing radiation is clearly

carcinogenic when presented at unusually high doses, but it has been

difficult to quantify its effect when presented at low doses. Because the

assumption is that any amount of exposure has some effect, federal

regulations mandate that exposure to radiation be kept “as low as

reasonably achievable.”

News Alert! Cancer and UV Light. Students should be able to suggest

that exposure to UV light damages genes that regulate the cell cycle.

The relationship between sun exposure and skin cancer has been clarified

Steps 6 and 7 provide

greatly across the past century. In the late 1800s, observers noticed that

excellent opportunities to

sailors exposed to the sun developed a variety of abnormal lesions called

assess students’

“sailor’s skin,” and in the early 1900s, an increased risk of skin cancer

was observed among farmers. By 1928, researchers had demonstrated

understanding of the

the carcinogenic effect of UV radiation on the skin of laboratory animals.

activity’s major concepts. In

Today, scientists recognize excessive exposure to UV radiation (whether

Step 6, students should be

from the sun or other sources) as a key risk factor for skin cancer.

able to express five key ideas

about the regulation of cell

8. Close the lesson by asking students what the activity reveals about science’s

division, and in Step 7, they

ability to bring order to even the most bewildering set of observations.

should be able to apply this

understanding to explain

Students should recognize that science helps us explain and relate

how certain risk factors

observations that we make about the natural world. You may wish to

increase a person’s chance of

ask students if they can think of other examples of observations that

developing cancer.

have been organized and made comprehensible through the work of

science. Students may propose the atomic theory, the cell theory, and

the germ theory of disease as important organizing explanations in

science. If they do not mention evolution, point out that evolution is

the most important organizing explanation in biology.

70

Lesson 2 Organizer: WEB VERSION

What the Teacher Does

Page and Step

Introduce the lesson by noting that people have wondered about

Page 65

the cause of cancer for thousands of years and have noticed many

Step 1

correlations between the development of cancer and various factors.

Give each student a copy of Master 2.1. Ask students to work

Page 65

in their groups to watch each of the News Alert! videos and to

Step 1

complete Section 1 of the master.

Ask students what each video suggests about the cause of cancer and

Page 65

what evidence supports the claims.

Step 2

Explain that each news item describes a real relationship between the

Page 66

development of cancer and the factor described. Ask students what

Step 3

general question all four videos raise when considered collectively.

Explain that research has helped scientists understand how so many

Page 66

different factors can cause cancer. Explain that students will

Step 4

• view animations to help them construct an explanation of the cause

of cancer and

• use their understanding of cancer’s cause to explain relationships in

the News Alert! videos.

Direct students to watch the online cell-cycle animations. Ask them to

Page 66

then complete Section 2 on Master 2.1.

Step 5

Point out that their five statements constitute a basic explanation of

Page 68

what goes wrong when a cell becomes cancerous. Ask one or more

Step 6

groups to read their statements to the class. Invite clarifying questions

and comments from other students.

Ask students to review Section 1 and then complete Section 3 of

Page 69

Master 2.1.

Step 7

Close by asking students what the activity reveals about science’s

Page 70

ability to bring order to the most bewildering set of observations.

Step 8

= Involves copying a master.

= Involves using the Internet ( http://science.education.nih.gov/supplements/nih1/cancer/

activities/activity2_videos.htm).

71

Student Lesson 2

Cell Biology and Cancer

Lesson 2 Organizer: PRINT VERSION

What the Teacher Does

Page and Step

Introduce the lesson by noting that people have wondered about

Page 67

the cause of cancer for thousands of years and have notices many

Step 1

correlations between the development of cancer and various factors.

Give each student a copy of Master 2.2. Ask students to work in their Page 67

groups to read each of the News Alert! items. Then give students one

Step 1

copy each of Master 2.1 and ask them to complete Section 1.

Ask students what each item suggests about the cause of cancer and

Page 67

what evidence supports the claims.

Step 2

Explain that each new item describes a real relationship between the

Page 67

development of cancer and the factor described. Ask students what

Step 3

general question all four items raise when considered collectively.

Explain that research has helped scientists understand how so many

Page 68

different factors can cause cancer. Give each student one copy of

Step 4

Master 2.3. Explain that the five resources will help them

• construct an explanation of the cause of cancer and

• use their understanding to explain relationships in the

News Alert! items.

Direct students to read Master 2.3 and then complete Section 2 on

Page 68

Master 2.1.

Step 5

Point out that their five statements constitute a basic explanation of

Page 68

what goes wrong when a cell becomes cancerous. Ask one or more

Step 6

groups to read their statements to the class. Invite clarifying questions

and comments from other students.

Ask students to review Section 1 and then complete Section 3 on

Page 69

Master 2.1.

Step 7

Close the lesson by asking students what the activity reveals

Page 70

about science’s ability to bring order to the most bewildering

Step 8

set of observations.

= Involves copying a master.

72

index-81_1.jpg

L E S S O N 3

Explain

Cancer as a

Multistep Process

Focus

At a Glance

Students use random-number tables and an online simulation

(or print-outs from a computer-based hit simulator) to test several

hypotheses about the development of cancer.

Major Concepts

No single event is enough to turn a cell into a cancerous cell.

Instead, it seems that the accumulation of damage to a number

of genes (“multiple hits”) across time leads to cancer.

Objectives

After completing this lesson, students will

• understand that cancer results from the accumulation of genetic

damage to cells across time and

• be able to explain the increase in cancer incidence that occurs with

an increase in age in terms of a multiple-hit (mutations in a number

of genes) hypothesis for cancer’s development.

Prerequisite Knowledge

Students should be familiar with the concepts taught in Lessons 1

and 2. Students should also have a basic knowledge of probability.

Step 6 describes a short exercise you can do with students to remind

them of the laws of probability.

Basic Science–Public Health Connection

This lesson highlights the contribution epidemiology has made to our

understanding of cancer. Students discover how analyzing the frequencies

of cancer provides compelling, though indirect, evidence that human

cancer is a multistep process. Students then consider the implications

of this understanding of cancer for personal and public health.

Estimated Time: 45–90 minutes

The process by which a normal cell is transformed into a malignant cell

Introduction

involves many changes. Cancer cells display a host of striking differences

from their normal counterparts, such as shape changes, changes in their

dependence on growth factors, and a multitude of biochemical differences.

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Cell Biology and Cancer

One of the earliest questions scientists asked about these phenotypic

differences was, how are they generated? Another question was whether

these differences arise all at once, at a moment when the cell experiences

a sudden, catastrophic shift from “normal” to “malignant,” or gradually,

across time, as a result of many small events, each contributing yet another

characteristic to a set that, in sum, gives the cell a malignant phenotype.

In this lesson, students examine some of the epidemiologic data that

suggest that the development of cancer is a multistep process. Students

study a graph of colon cancer incidence by age, answer an initial set of

questions about the relative risk of developing colon cancer at various ages,

and propose answers to the question of why this risk increases with age.

Students then use random-number tables and an online simulation (or

print-based alternative) to test several hypotheses about the development

of colon cancer (for example, colon cancer develops as a result of a single

event within a cell, colon cancer develops as a result of two independent

events within a cell, and so on). Finally, students use their understanding of

the development of cancer as a multistep process to explain 1) the increased

incidence of cancer with age, 2) the development of cancer decades after

exposure to known carcinogens, and 3) the increased incidence of cancer

among people with inherited predispositions.

Web-Based Activities

In Advance

Step 15.

Materials and Preparation

Photocopies and Transparencies

Equipment and Materials

• 1 copy of Master 3.1 for each

• (Optional) Computers with

student and 1 transparency

access to the Internet

• 1 copy of Master 3.2, cut up

• coins (1 penny, 1 nickel, and

so that each student gets one

1 dime for each student, only

data set

if you plan to conduct the

• 1 transparency of Master 3.3

review of probability described

• 1 copy of Master 3.4 for each

in Step 6)

student and 1 transparency

• a hat (or other container) with

• 1 copy of Master 3.5 for

folded slips of paper containing

each student

the numbers from 1 to 25

• 1 copy of Master 3.6 for

each student*

• 1 copy of Master 3.7 for

each student

* Needed only by classes without access to the Internet.

Follow the instructions on page 17 to get to the Web site on the computers

students will use. If you don’t have enough computers with Internet access,

you can use the print-based alternative for Step 15 (on page 80).

74

1. Open the activity by reminding students of the increase in cancer

Procedure

incidence with age that they observed in Lesson 1. Explain that in

Estimated time:

this activity, they will investigate the biological basis for this increase.

75–90 minutes

It is very important to set this lesson in the context of Lessons 1 and 2.

Without this context, students may complete this activity “by rote” and

never see how it relates to our growing understanding of the biological

basis of cancer.

2. Give each student one copy of Master 3.1, Colon Cancer Incidence by

Age, and ask the students to work in pairs to answer the questions

below the graph. (Data are from http://www.seer.cancer.gov.)

Give students about 5 minutes to complete this task.

3. Project Master 3.1 and invite the students to share their answers to

the questions.

Question 1. How likely is it that you will develop colon cancer this year?

Students should answer that the risk is so low that they cannot read it

from the graph. You may wish to ask whether children under 15 ever

develop colon cancer. In fact, those few children who do get colon

cancer have genetic conditions that predispose them to the development

of cancer.

Question 2. How likely is it that someone who is 60 years old will develop

colon cancer this year?

The risk is significantly higher (about 70 per 100,000 people).

Question 3. How likely is it that someone who is 80 years old will develop

colon cancer this year?

This risk is even higher (about 350 per 100,000 people).

Question 4. How can we explain this change in the risk of a person

developing colon cancer?

Answers will vary. Students may suggest that as people age, they

become more susceptible to cancer. Some may also suggest that it

takes time for the mutations involved in the development of cancer

to accumulate. Accept all reasonable answers, explaining that in

this lesson, students will have a chance to test a possible answer

to this question.

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Student Lesson 3

Cell Biology and Cancer

4. Circle the last question on the transparency or write it on the board,

and point out that this question is the central issue in this lesson.

Explain that many years ago, epidemiologists recognized that this

change in cancer risk provided an important clue about the cause

of cancer. This lesson challenges students to retrace the thinking

of these scientists and discover this clue for themselves.

If students are unfamiliar with the term “epidemiology,” explain that it

is the study of the incidence of disease in a population.

5. Remind students that one way scientists answer questions is by

developing and testing hypotheses, or tentative explanations. For

example, one explanation that might be offered for the development

of cancer might be summarized as, “One mutation in a certain gene in

a cell causes that cell to become cancerous” (the one-hit hypothesis).

Another explanation might be summarized as, “Two mutations

in separate genes of a cell are required before the cell becomes

cancerous” (the two-hit hypothesis), and so on. Ask students if they

can tell by looking at the colon cancer graph which of these two

explanations for the development of cancer best explains the data.

Students likely will answer that they cannot tell just by looking at

the graph.

6. Explain further that scientists often use models to test their

explanations. In this lesson, students will use two simple models,

one involving random-number tables and the other using an online

simulation (or print-outs from a computer-based hit simulator), to

test several alternate explanations for the development of cancer.

If your students are not familiar with some of the basic concepts of

probability, you may wish to conduct the following short exercise:

Give each student a penny, a nickel, and a dime, and ask students

to toss each coin one time and leave the coins lying on their

desks where they landed. Ask the students to raise their hands if

they got a “heads” on their penny. Count the number of students

who raise their hands and point out that this represents about

50 percent of the class. Then, ask students to indicate how many

got heads on both their penny and their nickel. Again, count the

number of students who raise their hands and point out that

this value is close to 25 percent of the class. Finally, ask students

to raise their hands only if they got a heads on all three of their

coins (the penny, the nickel, and the dime). This number should

be about one-eighth of the class. Ask students what pattern they

see in these data. Students should see that the probability of

independent events happening together is lower than each event’s

individual probability. Use your judgment to decide whether

to explain to students how to calculate the probability of such

occurrences (for example, the probability of getting heads on

three coins tossed individually is 1/2 × 1/2 × 1/2 = 1/8).

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7. Give each student one data set from Master 3.2, Random-Number

Tables, and explain that students will use these data to understand the implications of the following two hypotheses for the incidence of

cancer in a population (the class):

1. Cancer develops as a result of a single mutation (one-hit hypothesis).

2. Cancer develops as a result of two independent mutations

(two-hit hypothesis).

8. Explain that the data sets the students hold are called random-number

tables and were made as a computer randomly chose numbers between

1 and 25 to correspond with the students’ imagined life spans. Explain

that the first column on the table represents the students’ ages, and

that the second and third columns on the table represent the numbers

the computer chose.

9. Conduct the following exercise:

• Ask a student to draw a number out of the hat and announce the

number to the class. Write the number on the board.

For example, imagine that the student drew the number 10.

• Explain that this number represents a mutation in Gene 1.

Ask students to examine the column labeled “Gene 1” on

their random-number table to determine whether they have

the number chosen. If they do, they should circle it and note

the age at which it occurred.

Students should look down the column labeled “Gene 1” for the first

occurrence of the “unlucky” number (in this example, 10). If the

number occurs more than once, they should ignore the second

(and any subsequent) occurrence.

• Ask another student to draw a number out of the hat and

announce it to the class. Write the number on the board.

For example, imagine that the student drew the number 4.

• Explain that this second number represents a mutation in

Gene 2. Ask students to examine the column labeled “Gene 2”

on their random-number table to determine whether they have

the second number chosen. If they do, they should circle it

and note the age at which it occurred.

Students should look down the column labeled “Gene 2” for the

first occurrence of the “unlucky” number (in this example, 4).

If the number occurs more than once, they should ignore the

second (and any subsequent) occurrence.

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Student Lesson 3

Cell Biology and Cancer

10. Project Master 3.3, Collecting the Data, and explain that you are going to use this table to tally the number of people in the class who

would have developed cancer at each age if the one-hit or the two-hit

hypothesis for the development of cancer was true.

Explain that to discover the number of people who would have

developed cancer, the students need to examine their random-number

tables according to the following instructions:

• Tell students that first, the class is going to approximate what

might happen if the one-hit hypothesis were true (that is, if

one mutation were sufficient to cause a normal cell to become

cancerous). Ask students to imagine that if they found the first

“unlucky” number in the column labeled “Gene 1,” it meant a

gene in one of their cells experienced a cancer-causing mutation.

Explain that if the one-hit hypothesis is correct, the age at which

the unlucky number first appears in the column labeled “Gene 1”

would be the age at which they developed colon cancer.

Note that some students likely will not encounter the unlucky number

and, therefore, will not develop cancer.

• Poll the class to determine how many students developed

cancer under this model at each age (5–100 years) and add this

information to the column