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Semester 2 Molecular Medicine > Carcinogens > Flashcards

Carcinogens Flashcards

1
Q

What are the 4 major categories of carcinogens?

A
  • Chemicals
  • Radiation
  • Some parasites, fungal toxins e.g. aflatoxin
  • Viruses
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2
Q

What is the mechanism of chemical carcinogens?

A

Normal tissue –> (INITIATION) Altered genotype of an ‘initiated cell’–> (PROMOTION) New phenotype emerges resulting in clonal expansion of initiated cell –>(PROGRESSION) Malignant metastases
(MALIGNANCY)

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3
Q

What is meant by initiation?

A

(Mutagenic) event involves cellular genome mutations in tumour supressor genes and oncogenes

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4
Q

What is meant by promotion?

A

Promotion is reversible and not mutagenic and stimulates proliferation and causes both mutated and normal cells to proliferate.

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5
Q

What is meant by progression?

A

An irreversible enhancement/repression of gene expression.

Selection of neoplastic cells for optimal growth genotype/phenotype in response to the cellular environment

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6
Q

What will happen if somebody is exposed to a high does of carcinogen?

A

Tumours will develop (the carcinogen will act as both an initiator and promotor)

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7
Q

What will happen if someone is exposed to a low dose of carcinogen?

A

No tumours develop

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8
Q

What will happen if someone is exposed to multiple doses of promoter

A

No tumours develop

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9
Q

Low dose carcinogen and promotor

A

Tumours will develop

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10
Q

What is 2-napthylamine and what is it linked to?

A
  • Compound used in dyes

* Carcinogenic compound linked to bladder cancer

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11
Q

How does 2-Napthylamine act as a carcinogen?

A
  • Exists as an aromatic amine which is a pre-carcinogen requiring activation
  • The liver converts 2NTA to carcinogenic metabolite 2-amino-naphthol
  • 2 amino-naphthol is detoxified to glucuronide (not a carcinogen) which is then excreted by the kidneys
  • In the bladder, human urothelial cells express B-glucuronidase which converts the glucuronide to a carcinogen
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12
Q

What is asbestosis?

A

Formation of scar tissue in the lung as a result of exposure , predisposes to bronchogenic carcinomas

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13
Q

What does exposure of blue asbestos carry a risk for?

A

Mesothelioma

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14
Q

What is asbestos?

A

A fibrous silicate substance

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15
Q

What happens to asbestos when it is inhaled?

A

The needle-like fibres become coated in proteins (asbestos bodies) and their presence excites a macrophage and giant cell response

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16
Q

What is mesothelioma?

A
  • Rare tumour
  • Metastic spread is uncommon
  • Bulky tumour that can fill the chest cavity
17
Q

What is the active carcinogen in tobacco smoke?

A

Benzopyrene (polycyclic aromatic hydrocarbon 3,4-benzpyrene)

18
Q

Describe the effect of Benzopyrene

A

Leads to Guanine mutations in K-Ras and p53 in the regions found to be mutated in smoking induced lung cancer s

19
Q

What are the genes most frequently found to be mutated in smoking related lung cancers?

A

K-Ras and p53

20
Q

How does benzopyrene cause damage?

A

• Converted byAryl Hydrocarbon Hydroxylase (AHH) in to benzo[a]apyrene diol epoxide which binds to DNA forming damaging adducts

21
Q

What is unregulated in smokers putting them at a greater risk of lung cancer?

A

AHH (Aryl Hydrocarbon Hydroxylase) (in heavy smokers that do not develop lung cancer, AHH may not be expressed)

22
Q

Aside from lung cancer, which cancers are there increased risk of developing in smokers?

A
  • Oesophageal cancer
  • Bladder
  • Kidney
  • Pancreas
23
Q

What can secondary carcinogenesis occur from?

A

Alkylating agents in chemotherapy

24
Q

What can secondary tumours develop from following cancer treatment?

A
  • DNA damage inflicted on surviving normal somatic cells during treatment
  • DNA strand-breakage and base damage induced
25
Q

What risks do nitrites and nitrates carry?

A
  • Pathway for the conversion of dietary nitrites and nitrates to carcinogens
  • food additives and fertilisers that enter drinking water means it enters into the diet
  • Gut bacteria convert nitrites and nitrates into nitrosamines- carcinogens that can lead to cancers of the GI tract and liver
26
Q

What is Aflatoxicosis?

A

Poisoning, especially of the liver that results from the ingestion of aflatoxins from contaminated food

27
Q

What is Aflatoxin B1

A

A potent carcinogen in both human and animal species which can predispose to liver cancer - p53 mutation

28
Q

What is there such a large difference between the incidence of tumours in the large intestine and the small intestine?

A
  • Bcl2 is expressed in colonic epithelium and protects damaged cells from dying
  • Therefore cells survive and accumulate mutations, leading to carcinogenesis
  • Bcl2 is not expressed in the crypts of the small intestine
29
Q

What is UV radiation?

A
  • Non-ionising

* Damages DNA and forms pyrimidine dimers but can also break DNA by indirect mechanisms

Semester 2 Molecular Medicine (27 decks)

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