Lecture 7

Question 0

Where do somatic mutations occur? Are they heritable?

Answer 0

Non-germline tissues; non-heritable

Question 1

What are the three types of mutations?

Answer 1

Single base substitution, insertion, deletion

Question 2

Where do germline mutations occur? Are they heritable?

Answer 2

Egg or sperm; are heritable

Question 3

What mutation causes cancer family syndrome?

Answer 3

Germline mutations

Question 4

Do most cancers arise from somatic or germline mutations?

Answer 4

Somatic

Question 5

Are acquired mutations found in some or all cells of the body?

Answer 5

Some

Question 6

What are some internal factors that can damage DNA?

Answer 6

Depurination, deamination, reactive oxygen species

Question 7

When and where does depurination occur?

Answer 7

Spontaneously; in aqueous solution

Question 8

What does depurination result in?

Answer 8

An abasic site (loss of nucleotide base)

Question 9

When and where does deamination occur?

Answer 9

Spontaneously and under neutral pH

Question 10

What does deamination result in?

Answer 10

Changes in DNA sequence (mutation), unless repaired

Question 11

How do reactive oxygen species damage DNA?

Answer 11

Oxidation of nucleotide bases

Question 12

What three enzymes eliminate reactive oxygen species?

Answer 12

Superoxide dismutase, glutathione peroxidase, and catalase

Question 13

What reaction does superoxide dismutase catalyze?

Answer 13

Superoxide (O2-) –> hydrogen peroxide (H2O2)

Question 14

What reaction does glutathione peroxidase + catalase catalyze?

Answer 14

Hydrogen peroxide (H2O2) –> hydroxyl radical (OH-) –> water

Question 15

What is carcinogenesis?

Answer 15

Process by which normal cells are transformed into cancer cells

Question 16

What kind of DNA damage does UV radiation cause?

Answer 16

Covalent cross links between adjacent thymines –> thymine dimers

Question 17

What was the first discovered chemical carcinogen?

Answer 17

Benzo[a]pyrene (BP)

Question 18

Where is benzo[a]pyrene found, and what does it cause?

Answer 18

Found in chimney soot, tar, tobacco smoke, combustion products; causes Chimney sweep’s cancer

Question 19

What is the structure of benzo[a]pyrene?

Answer 19

Polycyclic aromatic hydrocarbon (PAH)

Question 20

What are the three major categories of carcinogens?

Answer 20

Alkylating agents, aralkylating agents, and arylhydroxyamines

Question 21

What do the three major classes of carcinogens have in common?

Answer 21

Compose 95% of all carcinogens, are electrophiles which will react with amines or double bonded oxygens, and they can covalently bind DNA

Question 22

What is a DNA adduct?

Answer 22

Piece of DNA covalently bonded to a carcinogen

Question 23

What are direct carcinogens?

Answer 23

Carcinogens that can readily and directly bind DNA

Question 24

What are indirect carcinogens?

Answer 24

Compounds that are not carcinogenic themselves, but can be turned into one in the body

Question 25

What are two examples of indirect carcinogens?

Answer 25

Benzopyrene and aflatoxin

Question 26

What is biotransformation?

Answer 26

Process by which the body modifies chemical toxins to make them more water soluble and thus increase the rate of its secretion

Question 27

Which enzymes are primarily responsible for biotransformation?

Answer 27

Cytochrome P450 enzymes

Question 28

Alkylation of DNA forms what structure?

Answer 28

A DNA adduct

Question 29

What is the Ames test?

Answer 29

Test using bacteria to screen for carcinogens that cause mutation

Question 30

How does tissue organization help prevent mutations?

Answer 30

Stem cells are located to the interior of the organ

Question 31

Proofreading of the genome is accomplished by what activity?

Answer 31

3'-5' exonuclease activity

Question 32

What two steps ensure replicative fidelity of the genome?

Answer 32

1. Selection of the correct nucleotide to be incorporated 2. Proofreading activity of polymerase

Question 33

What are melanosomes?

Answer 33

Granules (vesicles) containing melanin

Question 34

What does melanin protect against?

Answer 34

UV radiation

Question 35

What is the function of the glutathione S-transferase (GST) family of enzymes?

Answer 35

Catalyze the conjugation of glutathione to chemical compounds to help in detoxification

Question 36

What is glutathione a tripeptide of?

Answer 36

Glutamic acid, cysteine, and glycine

Question 37

What gives glutathione its detox ability?

Answer 37

Sulfhydryl group of cysteine

Question 38

What are the 3 phases of biotransformation?

Answer 38

1. Modification 2. Conjugation 3. Excretion

Question 39

What enzymes are responsible for biotransformation modification?

Answer 39

Cytochrome P450 class enzymes

Question 40

What enzymes are responsible biotransformation conjugation?

Answer 40

Glutathione S-transferase

Question 41

How can cells circumvent senescence (in culture)?

Answer 41

Expression of SV40 large T (LT) antigen

Question 42

What effect does SV40 LT antigen have in the cell?

Answer 42

Sequesters and inactivated tumor suppressor proteins pRB and p53

Question 43

Mutations in this gene can cause abnormal senescence

Answer 43

BRCA1

Question 44

Is inducing senescence alone enough to treat cancer cells?

Answer 44

No, cancer cells can circumvent senescence