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SSC- Biology of Cancer > Carciogenesis > Flashcards

Flashcards in Carciogenesis Deck (93)
1

What is cancer? 

A group of diseases all sharing similar characteristics

2

What are the characteristics that all cancers share? 

They are all abnormal, uncontrolled growths of cells. They all show inappropriate proliferation, invasion, and metastasis 

 

3

What are the characteristics of a benign tumour? 

  • Slow growth
  • Non-invasive
  • No metastasis

 

4

What are the characteristics of a malignant tumour?

  • Rapid growth
  • Invasive
  • Potential for metastasis

 

5

What is the increase in incidence of cancer due to? 

  • Lifestyle changes
  • Increased screening

 

6

What is carciogenesis? 

The process of transformation of a 'normal' cell to a cancer cell

7

What are the stages in carciogenesis? 

  1. Initiation
  2. Promotion
  3. Progression
  4. Transformation
  5. Evolution
  6. Metastasis

 

8

What happens in initiation? 

A mutation in stem cells is acquried when they are exposed to a carcinogen, and you get unrepaired DNA damage

9

What happens in promotion? 

There is induction of cell division, where the cancer starts from a single cell that has a selective advantage over other cells within the same tissue 

10

How does promotion lead to progression? 

Increased proliferation means increased mutations and therefore an increased advantage

11

What happens in progression? 

  • Conversion
  • Propagation
  • Dedifferentiation 

 

12

What is there a potential for in transformation? 

Regression

13

What can be produced in cancer evolution?

A drug resistant clinical tumour 

14

What happens in cancer metastasis? 

Spread of transformed cells 

15

What stages of carciogenesis can be used to treat cancer? 

Can enter at any stage to try and prevent disease

16

What does mutation lead to in colorectal carciogenesis? 

Inactivation of the APC gene 

17

What will an inactivation of the APC gene in colorectal carcinogenesis cause? 

May cause a change in frequency in division, which leads to an increase in stem cells. This will develop over time into a cluster of APC-less cells with stem cell properties 

18

What might the 'second hit' be in colorectal carcinogenesis? 

Inactivation of Ras

19

What is the result of the inactivation of Ras in colorectal carcinogenesis? 

Increased selective advantage 

20

What might the third hit be in colorectal carcinogenesis? 

Inactivation of p53

21

What happens after the third hit in colorectal carcinogenesis? 

Increased growth, starts to form an adenoma 

22

What does the forth hit in colorectal carcinogenesis lead to? 

The rapid development of cancer

23

What extracellular/environmental factors can cause genes to mutate? 

  • Binding of ultimate carcinogens
  • Ionising radiation/UV
  • DNA translocation

 

24

What do ultimate carcinogens do? 

Bind to DNA and alter the sequence

25

What effect does ionising radiation and UV have on DNA? 

Causes strand breaks and cross links

26

When may DNA translocation cause mutations? 

When it is translocation to transcriptionally active regions

27

What intracellular factors can cause mutations? 

  • Misinterpretation of code
  • Polymerase slippage/base misalignment
  • Ineffective repair

 

28

What can all mutations potentially affect? 

Cellular signalling

29

What can act as initiating stimuli in carcinogenesis?

  • Chemical carcinogens
  • Oncogenic viruses
  • Radiation
  • UV light
  • Oxygen free radicals
  • Replication errors

 

30

When can oxygen free radicals act as an initiating stimuli for carcinogenesis? 

When there is an imbalance between their production (which happens naturally) and their removal 

31

What are the categories of directly acting carcinogens? 

  • Alkylating and acylating agents
  • Weak carcinogens 

 

32

Give three examples of alkylating or acylating agents that can act as carcinogens

  • Dimethylsulphate
  • Chlorambucil
  • Dichloromethane

 

33

What can act as a weak carcinogen?

Cytotoxic drugs

34

Give an example of a class of procarcinogens

Polycyclic aromatic hydrocarbons

35

When might polycyclic aromatic hydrocarbons be produced?

During the combusion of organic compounds, e.g coal, petrol, cooked foods, tobacco, smoke

 

 

36

What does exposure to polycyclic aromatic hydrocarbons typically cause tumours? 

Lung and colon

37

Where is aflatoxin found? 

In fungus found on peanuts and other foodstuffs

38

What are the steps in the metabolic toxification of aflatoxin? 

Aflatoxin B1 + Mfo --> Aflatoxin-2,3-epoxide

Alfatoxin-2,3-epoxide is highly reactive, so will react with DNA to form a DNA adduct

39

What does exposure to aflatoxin correlate to? 

The risk of liver cancer 

40

Where is liver cancer related to aflatoxin prevalent?

In hot regions

41

How can you determine aflatoxin exposure?

  • Can measure content in food
  • Can measure DNA adduct 

 

42

What happens to genes in cancer? 

  • Oncogenes are activated
  • Tumour supressor genes are inactivated

 

43

What mutations can occur to a gene? 

  • Alteration of bases
  • Strand break
  • Base oxidation
  • Deletion of bases
  • Adducts of carcinogens and base
  • Chromosomal translocation/rearrangement
  • Gene amplification

 

44

Describe the severity of different DNA strand breaks? 

If it's a single strand break, the body can normally repair it. Double strand breaks normally can't be repaired

 

 

45

How does an adduct mutation cause cancer? 

A chemical binds to the base, and so repair mechanisms either can't get part that point on the DNA, or don't know what base to replicate 

 

46

What mechanisms are in place to prevent mutations causing cancer? 

  • Repair mechanisms
  • Mismatch and excision repair
  • p53

 

47

What causes single point mutations? 

Mutagens

48

What are the type of single point mutations? 

  • Transitions
  • Transversions

 

49

What is a transition mutations? 

  • Purine -> purine (A -> G, G -> A) 
  • Pyrimidines -> pyrimidines (C -> T, T -> C)

 

50

What is a transversion mutation? 

  • Purine -> Pyramidine 
  • Pyramidine -> Purine

 

51

What causes structural chromosomal abberations? 

Clastogens

52

What structural chromosomal aberrations can occur? 

  • Translocations
  • Inversions
  • Deletions
  • Insertions
  • Chromatid interchanges

 

53

What causes genome mutations?

Aneugens

 

 

54

What is aneuploidy? 

An increase in the number of chromosomes in the cell

55

What is the most common nucleophilic binding site on DNA?

N7

56

Is N7 on guanine highly mutagenic or not? 

No, it is easily repaired 

57

What is the guanine N7 commonly used for? 

Monitoring

58

What guanine nucleophilic binding sites are highly mutagenic? 

N2 and N3

59

How does mutagenesis by adduct formation occur? 

  1. An adduct binds to the base 
  2. After the first replication, the adduct is maintained in the sequence for one copy
  3. After replication of the copy with the adduct, you get a different amino acid, resulting in a different protein and therefore different structure

 

60

What proportion of base changes result in pernament mutation? 

Fewer than 1:1000

61

What are the DNA repair pathways? 

  • Excision repair
  • Error-prone repair
  • Mismatch repair
  • Defects in DNA replication

 

62

What can be removed in excision repair? 

  • Base 
  • Nucleotide

 

63

What enzymes perform base excision? 

DNA glycosylases

64

What does nucleotide excision remove? 

Bases with bulky adducts

65

Is excision repair error prone or error free? 

Error free

 

66

What is error-prone repair a response to? 

Severe DNA damage

67

What happens in error-prone repair? 

Low fidelity DNA polymerases recognise specific lesions, and restore the original sequence 

Accepts error, but fixes gross changes

68

What is mismatch repair? 

Proofreading by exonuclease part of DNA polymerase

69

How does repair occur in mismatch repair? 

  • Correcting mismatched bases in new strand during DNA replication
  • Genetic recombination

 

70

How are defects in DNA replication used in repair? 

  • Genome rearrangements
  • Chromosome loss

 

71

What things can act as promoting agents? 

  • Chemical promoters
  • Hormones
  • Inflammation
  • Microbial infection

 

72

Give 4 classes of chemical promoters

  • Phorbol esters
  • Phenols
  • Xenoestrogens
  • Saccharin

 

73

Give three examples of where inflammation and infection can act as promoters

  • Chronic irritation
  • Endoparasites
  • Bacterial infection

 

74

Give an example of an endoparasite that can act as a promoter 

Schistosoma haematobium 

75

Give an example of a bacterial infection that can act as a promoter

Helicobacter pylori

76

What factors increase the risk of breast cancer? 

  • Older age at menopause
  • Post-menopausal hysterectomy
  • Oral contraceptives
  • Alcohol
  • Obesity
  • Younger age at menarche

 

 

77

What factors decrease the risk of breast cancer?

  • More children
  • Breastfeeding
  • Pre-menopausal hysterectomy

 

78

What factors increase the risk of getting cancer? 

  • Hereditary
  • Carcinogens
  • Radiation
  • Chemicals
  • Viruses
  • Diet

 

79

How can food act as carcinogens? 

  • Can contain carcinogens/mutagens
  • Can contain toxins
  • Calories can alter the hormone balance
  • Inflammation/oxidative stress inducers 
  • Hot drinks/food can cause inflammation in mouth and oesophagus

80

What foods increase the risk of cancers? 

  • Alcohol
  • Red meat intake
  • Animal fat
  • Salted fish
  • BBQ and chargrilled foods
  • Salt-preserved foods
  • Contaminated foods

 

81

What evidence is there for the link between certain foods and cancer? 

  • Migration studies
  • Intervention trials

 

82

What are the components of the diet? 

  • Macronutrients
  • Micronutrients
  • Other compounds; procarcinogens, promoters, alcohol 

 

83

What are the categories of macronutrients?

  • Fats
  • Carbohydrates
  • FIbres

 

84

What are the categories of micronutrients? 

  • Antioxidants
  • Carotenoids
  • Polyphenols

 

85

What does red meat consumption increase the risk of? 

Colon cancer

86

What effect does cooking red meat have on its carcinogenic risk? 

It increases the heterocyclic amine concentration by 50-100x. HA's are mutagenic. 

87

What happens to heterocyclic amines in the liver? 

They are metabolised to genotoxic metabolites 

88

What has shown heterocyclic amines to be mutagenic? 

Ames test 

89

What has shown heterocyclic amines to be carcinogenic? 

In vivo models

90

What can increase the HA levels in food? 

Increasing the cooking time 

91

What can reduce the HA levels in food? 

Marinating 

92

What are the sources of acrylamide? 

  • Used as drinking water clarifier
  • Found in cigarette smoke

 

93

What is the problem with acrylamide? 

It is a genotoxic metabolite, which adducts with DNA in vivo

However, the human evidence for cancer is scarce