Genetic Toxicology Flashcards
Define Genetic Toxicology.
The effects of chemical and physical agents on DNA and on the genetic processes or living cells
Define a Clastogen:
Induces chromosomal aberrations
Define a Mutagen:
Induces gene mutations
What happens when genetic alterations are made to: a) somatic cells, and b) germ cells?
a) cell death, senescence, cancer
b) effects on offspring
Name 5 of the 12 possible methods of DNA damage
Abasic sites Base adducts Thymidine Dimers Interstrand crosslinks Base insertions A-G mismatch T-C mismatch Mase deletions Double-strand breaks Chemical mutagens Single-strand Breaks Abnormal bases
Define a mutation hot spot
A stretch of DNA that is highly susceptible to mutation
What is EMS and what does it do?
Ethyl methanesulfonate, takes up one of the 3 binding sites on guanine allowing it to bind eg thymine
What is the consequence of a base pair addition/deletion
Frameshift
What are the 5 possible protein results of a mutated RNA
- no protein
- normal protein amounts
- too much protein
- shortened protein
- protein with mutation
What are the 4 types of DNA Repair?
Mismatch Repair system
Nucleotide excision repair system
Base excision repair system
Recombination repair system
Describe base excision repair
1) remove base
2) break one side of backbone
3) insert new backbone with appropriate base
4) remove original backbone
5) religate with new backbone
Describe Nucleotide Excision repair pathway
1) DNA dissociates from sister strand
2) entire segment of DNA removed
3) DNA pol synthesises new strand based on sister strand
Give an example of a disease that could occur with a dysfunctional NER pathway
Xeroderma pigmentosum
Homologous Recombination targets ____
Double Strand Breaks (strand invasion)
Nonhomologous End Joining targets ____
Double strand breaks
no other strand needed
Recombination might not be problematic unless ____
Important sequences are cleaved
What does SCE test for
Sister chromatid exchange
How does Mismatch repair work?
1) Backbone cleaved up and down stream of mismatch
2) entire segment is removed
3) new backbone synthesized and ligated
Direct reversal Mismatch repair uses ____
MGMT - methylguanine DNA methyltransferase*
* binds irreversably
True/False? If DNA damage does not get repaired, the best way to deal with it is to have the cell kill itself
True. If mutations don’t get detected, errors may ensue
What is p53’s function?
A tumor suppression gene
What happens when p53 is mutated?
p53 does not arrest the cell cycle when damage is present, tumor growth
True/False? Genetic polymorphisms are nonpathogenic
True
SNP stands for
Single Nucleotide Polymorphism
