Biology 12

290 MHR • Unit 3 Molecular Genetics

of nucleotides. Base analogues can be incorporated

into DNA, but they will pair incorrectly during

replication and cause substitution mutations. Other

chemical mutagens react with nucleotides with the

result that the shapes and bonding of the nucleotides

are changed. For example, some mutagens can

cause a C nucleotide to become a U nucleotide.

Still other chemicals can insert themselves into

the DNA double helix, causing distortions that

stall replication or result in frameshift mutations.

Examples of chemical mutagens include nitrites

(which are sometimes used as a food preservative),

gasoline fumes, and the benzene compounds found

in cigarette smoke.

The Ames testis a simple test that measures

the potential for a chemical to be mutagenic. As

illustrated in Figure 9.7, this test uses a mutant

strain of bacterium that is unable to synthesize the

amino acid histidine. A suspension of the mutant

bacteria is treated with the chemical and then spread

onto a medium that lacks histidine. Only those

bacteria that have undergone a reverse mutation—

that is, a second mutation that restores their ability

to synthesize histidine — will be able to grow. The

more mutations induced by the chemical, the more

likely it is that a reverse mutation will occur.

Therefore, the number of colonies of bacteria that

appear on the histidine-free medium indicates how

strong a mutagen the chemical is.

Most chemical mutagens are carcinogenic—

that is, they are associated with one or more forms

of cancer. For this reason, the Ames test is used by

many industries and government agencies as part

of the process of screening new products for

potential cancer-causing agents.

Cumulative Mutations

As you saw earlier, a single mutation often has

little or no effect on a living cell. Over the life of a

cell, however, a series of spontaneous and induced

mutations can add up to more serious damage. For

example, most cancers are the result of combinations

of mutations. Some of these may be inherited, while

others may arise as a result of exposure to mutagens

in the environment. The fact that mutations

accumulate within a cell helps explain why exposure

to chemicals that are known to be carcinogens does

not always result in cancer, and why cancer can

occur without exposure to any known carcinogens.

In the Thinking Lab on the following page, you

will have the opportunity to identify different

kinds of mutations and predict their effects.

Figure 9.7The Ames test was developed as a simple way

to test for mutagens. An extract of rat liver is added to the

chemical solution in order to simulate conditions inside a

mammalian body. Most mutagens are associated with

cancer, so the Ames test is an important part of consumer

safety screening processes.

incubation

at 37°C

after 48 h colonies

are counted and their

numbers are compared

rat liver

chemical extract

solution

histidine-

dependent

bacteria

histidine-free

medium

incubation

at 37°C

rat liver

extract

histidine-

dependent

bacteria histidine-free

medium

A solution containing the

chemical to be tested is added

to a culture of mutant

(histidine-dependent) bacteria

along with rat liver extract. The

bacteria are then cultured on a

histidine-free medium. Only

those that undergo a reverse

mutation will survive and

produce colonies.

A

A control is prepared by

treating a culture of the same

bacteria with a solution that

contains the rat liver extract

but not the chemical. A small

number of bacterial colonies

will appear due to spontaneous

mutations. The number of

colonies found in the

experimental sample is

compared to the number of

colonies in the control sample.

B