Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Carolyn's lectures > Genetic toxicology > Flashcards

Genetic toxicology Flashcards

1
Q

What is genetic toxicology?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What does DNA damage involve?

A
  • Chromosome breakage (clastogenesis)
  • Alteration of the DNA base sequence
  • Mis-segregation of chromosomes (aneugenesis)
  • Interchange of sections of chromosomes altering gene regulation (recombination)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is clastogenesis?

A

Chromosome breakage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is aneugenesis?

A

Mis-segregation of chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What do dominant mutation cause?

A

-they immediately cause disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What do recessive mutations cause?

A

-Mutations may be silent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the difference between germ cells and somatic cells?

A

Germ cells - produce gametes and undergo meiosis

Somatic cells - Other cells which undergo only mitosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the potential consequences if somatic cells undergo mutation?

A
  • Carcinogenicity

- Teratogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the consequences when germ cells undergo mutation?

A
  • Inherited genetic change

- Potential for reproductive toxicity (teratogenic. fertility), carcinogenicity or other genetic disorders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Teratogenicity can be caused by non genetic mechanisms. TRUE OR FALSE?

A

TRUE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How do drugs cause DNA damage?

A
  • The drug covalently binds to DNA (causing helix to twist)
  • The drug chemically modifies DNA bases e.g alkylate
  • The drug is incorporated instead of DNA base
  • Drug binds non covalently to DNA (e.g intercalators)
  • Strand breaks
  • Inter and intrastrand crosslinks
  • Crosslink DNA to protein
  • Drug interferes with DNA replication mechanisms
  • Potentially - drug interferes with DNA repair mechanism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Give examples of some DNA damaging agents?

A
  • X rays
  • Oxygen radicals
  • Alkylating agents
  • UV light
  • Replication errors
  • Spontaneous reactions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the consequences for DNA damage caused by damaging agents?

A

-Inhibition of transcription, replication, chromosomes segregation, mutation, chromosome aberrations (cancer, ageing and inborn disease)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are some of the repairing processes?

A
  • Base excision repair (BER)
  • Nucleotide excision repair (NER)
  • Recombinational repair
  • Mismatch repair
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Give an example of an intercalating agent?

A

Ethidium bromide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How do intercalating agents work?

A
  • They bind between DNA strands
  • Causing misalignment during replication
  • These can be sequence specific
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Biotransformation can render a drug more reactive and may create an electrophile. TRUE OR FALSE?

A

TRUE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe what occurs in mis-match repair?

A
  • It repairs mismatched bases
  • Damage is recognised by a specific protein that binds to the mismatch
  • It cuts DNA at a distance from mismatch
  • Excision past mismatch
  • Resynthesis and ligation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Describe what occurs in Base excision repair?

A
  • It removes damaged base
  • The gap left is filled by DNA polymerase
  • Followed by ligation to the parent DNA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe what occurs in Homologous recombination?

A
  • It repairs double strand breaks

- Single strand tail forms which invades an undamaged homologous chromatid and uses this as template to repair

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Describe what occurs in non-homologous end-joining ?

A
  • It repairs double strand break
  • Broken ends are directly ligated
  • No template so more error prone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Which of these two is more prone to errors during repair, Homologous recombination or non-homologous end-joining and provide reason for this?

A

Non-homologous end-joining - because there is no template

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the potential errors that can occur during DNA repair?

A
  • Repair enzymes may not determine which is the correct base
  • Excision repair polymerase - lower fidelity than in replication
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the consequences of errors?

A
  • Mutations within a single gene or within a restricted number of genes
  • Chromosomal aberrations
  • Genomic mutations
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Mutation outside coding region can affect gene expression if mutation occurs within a single gene. TRUE OR FALSE?

A

TRUE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is chromosomal aberrations?

A

Structural change in the chromosome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is genomic mutations?

A

Change in in number of chromosomes (aneuploidy)

28
Q

State the three types of single gene mutation and state the consequences that each one has?

A
  1. Base pair substitution - can obtain errors during replication/ wrong base
  2. Spontaneous base change - can be silent/missense or nonsense - this may have no effect/intermediate effect or drastic effect on protein function
  3. Addition and deletion of bases - Can occur during DNA repair or during replication (e.g intercalating agent) - can cause frameshift and is potentially devastating
29
Q

Spontaneous base changes may be important with drugs which interfere with DNA repair. TRUE OR FALSE?

A

TRUE

30
Q

addition and deletion of bases can have a wild type and mutant type effect. TRUE OR FALSE?

A

TRUE

31
Q

What causes chromosomal strands to break during chromosomal aberrations?

A

Ionizing radiation

32
Q

What drugs cause strands to break in chromosomal aberrations?

A

E.g Bleomycin , topoisomerase inhibitors

33
Q

Drug induced strand breaks do not result from error in DNA synthesis suing damaged template or repair of bulky adduct. TRUE OR FALSE?

A

FALSE

34
Q

What does break in DNA create?

A

-Creates cohesive end causing fragments to rejoin inappropriately

35
Q

What is aneuploidy?

A

Altered number of chromosomes

36
Q

What is polyploid?

A

Extra copy of complete set of chromosomes (4n tetraploid)

37
Q

What are the causes of genomic changes?

A
  • (any drug affecting chromosome replication or chromatid segregation will cause genomic changes)
  • Drugs affecting nuclear spindle microtubules eg paclitaxel, colchicine
38
Q

Cohesive ends can be loss of part of chromosome/amplification of part of chromosome etc. TRUE OR FALSE?

A

TRUE

39
Q

Anticancer drugs cannot increase the likelihood of a different type of cancer. TRUE OR FALSE?

A

FALSE

40
Q

Anticancer drug such as paclitaxel and carboplatin (used to treat ovarian cancer) can increase chances of acquiring what other type of cancer?

A

Leukemia

41
Q

Anticancer drug Melphalan (used to treat breast cancer) increases chances if acquiring what type of cancer?

A

Leukemia

42
Q

Carcinogens cause mutation within a single gene. TRUE OR FALSE?

A

TRUE

43
Q

What are primary carcinogens?

A

Can cause mutation

44
Q

What are secondary carcinogens?

A

Require biotransformation to cause mutation

45
Q

What do co-carcinogens do?

A

Enhances ability of carcinogen to cause mutation

46
Q

Carcinogens cause mutations within a single gene. TRUE OR FALSE?

A

TRUE

47
Q

Initiated cells have no clear morphological change. TRUE OR FALSE?

A

TRUE

48
Q

What do tumour promoters do?

A

They promote the development of cancer after mutation

49
Q

Tumour promoters do not cause disease on own but cause increased incidence and decrease latency. TRUE OR FALSE?

A

TRUE

50
Q

Are tumour promoters reversible or irreversible?

A

Reversible, mutation is not required (epigenetic)

51
Q

Tumour promoters do not cause proliferation of initiated cells. TRUE OR FALSE?

A

FALSE

52
Q

Carcinogen mutations are irreversible. TRUE OR FALSE?

A

TRUE

53
Q

Some compounds are both initiators and promoters. TRUE OR FALSE?

A

TRUE

54
Q

What occurs in the progression phase of the “chemical carcinogenesis model”?

A
  • Becomes clinical observable (neoplasia)
  • Genomic instability
  • Chromosomal aberrations and genomic mutations
  • Develops into maligant form
  • Becomes invasive with high mitotic index and becomes metastatic
55
Q

What are the different phases of the chemical carcinogenesis model?

A
  • Initiation (initial damage)
  • Promotion (expansion)
  • Progression (uncontrolled growth)
56
Q

What occurs when oncogenes are activated?

A
  • Mutation of oncogene itself
  • Increased expression of the oncogene due to genetic changes in regulatory elements
  • Amplification of gene
  • Translocation to fuse with a highly expressed gene
57
Q

What occurs when tumour suppressors are inhibited?

A
  • Mutation is inactivated
  • There is a decreased expression of the oncogene due to genetic changes in regulatory elements
  • Deletion of the gene
  • Translocation to separate from an active promoter
58
Q

What are teratogens?

A

-This is an agent (drug) which when administered to a woman or sometimes to a man causes structural or functional abnormalities in a foetus

59
Q

Give some examples of teratogens and their effects?

A
  • Alcohol : Fetal alcohol syndrome
  • Anti cancer agents : multiple congenital defects
  • Tetracycline : yellow teeth, inhibition of bone growth
  • Warfarin : multiple congenital defects
60
Q

What are the 8 mechanisms for teratogenesis?

A
  • Mutations within a single gene
  • Chromosome aberrations
  • Genomic changes
  • Enzyme inhibition
  • Receptor antagonism
  • Altered cell-cell interactions
  • Altered metabolism. reduced energy supply
  • Alteration of cell migration
61
Q

Teratogenesis is not just genetic toxicity. TRUE OR FALSE?

A

TRUE

62
Q

Toxic drugs are likely to cause spontaneous abortion. TRUE OR FALSE?

A

TRUE

63
Q

What trimester during pregnancy is the most critical that toxic drugs can cause structural abnormalities?

A

First trimester

64
Q

During the second and third trimester, toxic drugs affect growth, maturation and integrity of structures. TRUE OR FALSE?

A

TRUE

65
Q

Organogenesis is the most critical period. TRUE OR FALSE?

A

TRUE

66
Q

The period of most susceptibility to damage coincides with the development of each structure. TRUE OR FALSE?

A

TRUE

Carolyn's lectures (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions