Genetic toxicology Flashcards
Define Genetic toxicology
The study of genetic damage that results in alterations to heritable information
What may DNA damage involve?
- Chromosome breakage (clastogenesis)
- Alteration of DNA base sequence (Mutagenesis)
- Mis-segragation of chromosomes
- Interchange of sections of chromosomes (altering gene regulation)
State the difference between Dominant and Recessive mutation
Dominant mutation = may immediately cause disease
Recessive mutation = may be silent
Describe the first 3 steps of how drugs cause DNA damage
1) Drugs binds covalently to DNA
2) Drug chemically modifies DNA bases
3) Drug is incorporated instead of DNA base
Describe the second 3 steps of how drugs cause DNA damage
4) Drug then binds non-covalently to DNA
5) DNA strand breaks
6) Inter and Intra strand crosslink
Describe the final 2 steps of how drugs cause DNA damage
7) DNA and Protein crosslink
8) Drug interferes w/DNA replication mechanism
(may also interfere with repair mechanism)
What is a Teratogen ?
An agent which when administered to a woman causes structural or functional abnormalities in a foetus
When do drugs cause reproductive
toxicity (teratogenicity)?
the 1st trimester
Intercalating agents bind b/wn DNA strands. TRUE or FALSE
TRUE
Give an example of an intercalating agent
Ethidium bromide
Biotransformation can make a drug more reactive. TRUE or FALSE
TRUE
Biotransformation may create an electrophile. TRUE or FALSE
TRUE
Give an example of an intercalating and strand cleaving molecule
Esperamicin
Name 5 types of DNA repair
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)
State 2 errors that may arise from DNA repair
1) Repair enzymes may not be able to determine which is the correct base
2) Excision repair polymerase = lower fidelity than in replication
Chromosomal abberations result from strand breaks. TRUE or FALSE
TRUE
Ionizing radiation cannot cause double strand break. TRUE or FALSE
FALSE. It can cause double strand break
Name a drug that directly causes strand break
Bleomycin
How may drugs cause genetic mutation
Drug affects nuclear spindle microtubules
Give 4 examples of drugs that may cause genetic mutation
- Paclitaxel
- Vincristine
- Vinblastine
- Colchicine
State the 3 stages of chemical carcinogenesis
1) Initiation (Initial damage)
2) Promotion (expansion)
3) Progression (uncontrollable growth)
Do primary or secondary carcinogens require biotransformation to cause mutations ?
Secondary carcinogens
Co-carcinogens enhance carcinogen ability to cause mutation. TRUE or FALSE
TRUE
During Initiation stage of carcinogenesis, what is activated and what is inhibited ?
Oncogenes are activated
Tumour suppressors are inhibited
