Genetic toxicology

Question 1

Define Genetic toxicology

Answer 1

The study of genetic damage that results in alterations to heritable information

Question 2

What may DNA damage involve?

Answer 2

• Chromosome breakage (clastogenesis)
• Alteration of DNA base sequence (Mutagenesis)
• Mis-segragation of chromosomes
• Interchange of sections of chromosomes (altering gene regulation)

Question 3

State the difference between Dominant and Recessive mutation

Answer 3

Dominant mutation = may immediately cause disease

Recessive mutation = may be silent

Question 4

Describe the first 3 steps of how drugs cause DNA damage

Answer 4

1) Drugs binds covalently to DNA
2) Drug chemically modifies DNA bases
3) Drug is incorporated instead of DNA base

Question 5

Describe the second 3 steps of how drugs cause DNA damage

Answer 5

4) Drug then binds non-covalently to DNA
5) DNA strand breaks
6) Inter and Intra strand crosslink

Question 6

Describe the final 2 steps of how drugs cause DNA damage

Answer 6

7) DNA and Protein crosslink
8) Drug interferes w/DNA replication mechanism
(may also interfere with repair mechanism)

Question 7

What is a Teratogen ?

Answer 7

An agent which when administered to a woman causes structural or functional abnormalities in a foetus

Question 8

When do drugs cause reproductive

toxicity (teratogenicity)?

Answer 8

the 1st trimester

Question 9

Intercalating agents bind b/wn DNA strands. TRUE or FALSE

Answer 9

TRUE

Question 10

Give an example of an intercalating agent

Answer 10

Ethidium bromide

Question 11

Biotransformation can make a drug more reactive. TRUE or FALSE

Answer 11

TRUE

Question 12

Biotransformation may create an electrophile. TRUE or FALSE

Answer 12

TRUE

Question 13

Give an example of an intercalating and strand cleaving molecule

Answer 13

Esperamicin

Question 14

Name 5 types of DNA repair

Answer 14

1) Direct repair (e.g: via demethylation)
2) Mis-match repair (MMR)
3) Base excision repair (BER)
4) Homologous recombination (HR)
5) non-homologous end-joining (NHEJ)

Question 15

State 2 errors that may arise from DNA repair

Answer 15

1) Repair enzymes may not be able to determine which is the correct base
2) Excision repair polymerase = lower fidelity than in replication

Question 16

Chromosomal abberations result from strand breaks. TRUE or FALSE

Answer 16

TRUE

Question 17

Ionizing radiation cannot cause double strand break. TRUE or FALSE

Answer 17

FALSE. It can cause double strand break

Question 18

Name a drug that directly causes strand break

Answer 18

Bleomycin

Question 19

How may drugs cause genetic mutation

Answer 19

Drug affects nuclear spindle microtubules

Question 20

Give 4 examples of drugs that may cause genetic mutation

Answer 20

• Paclitaxel
• Vincristine
• Vinblastine
• Colchicine

Question 21

State the 3 stages of chemical carcinogenesis

Answer 21

1) Initiation (Initial damage)
2) Promotion (expansion)
3) Progression (uncontrollable growth)

Question 22

Do primary or secondary carcinogens require biotransformation to cause mutations ?

Answer 22

Secondary carcinogens

Question 23

Co-carcinogens enhance carcinogen ability to cause mutation. TRUE or FALSE

Answer 23

TRUE

Question 24

During Initiation stage of carcinogenesis, what is activated and what is inhibited ?

Answer 24

Oncogenes are activated

Tumour suppressors are inhibited