Carcinogenesis

Question 1

what is initiation?

Answer 1

+ mutagenic

+ cellular genome mutations in tumour suppressor genes and oncogenes

Question 2

what is a carcinogen?

Answer 2

A substance or agent that can cause cells to become cancerous by altering their genetic structure

Question 3

what is promotion (acceleration)?

Answer 3

+ reversible, not mutagenic

+ stimulates proliferation and causes both mutated and normal cells to proliferate

e.g TPA (phorbol esters), dioxin (polycyclic aromatic compounds)

Question 4

what is progression?

Answer 4

+ irreversible enhancement/repression of gene expression

+ selection of neoplastic cells for optimal growth genotype/phenotype in response to cellular environment

Question 5

what is the latent period?

Answer 5

the amount of time that elapses between initial exposure and diagnosis of cancer

Question 6

what cancer is 3,4-benzpyrene associated with?

Answer 6

scrotal cancer

Question 7

which carcinogenic substance is associated with scrotal cancer?

Answer 7

3,4-benzpyrene

Question 8

what carcinogenic substance was associated with bladder cancer?

Answer 8

2-napthylamine (2NTA)

Question 9

what cancer is 2-napthylamine (2NTA) associated with?

Answer 9

bladder cancer

Question 10

describe the mechanism of cancer induction in the liver by napthylamine?

Answer 10

+ liver converts 2NTA to carcinogenic metabolite 2-amino-naphthol
+ detoxified to glucuronide (not carcinogenic)
+ excreted by kidneys

Question 11

describe the mechanism of cancer induction in the bladder by napthylamine?

Answer 11

+ human urothelial cells express β-glucuronidase

+ converts glucuronide to a carcinogen

Question 12

what form of cancer is associated with asbestos?

Answer 12

+ bronchiogenic carcinomas

+ ‘blue’ asbestos fibres: mesothelioma

Question 13

what type of substance is asbestos?

Answer 13

fibrous silicate

Question 14

what are features of the mesothelioma from asbestos?

Answer 14

+ dense white sheet
+ metastatic spread uncommon
+ bulky tumour that can fill chest cavity

Question 15

what are the two genes more frequently mutated in smoking-related lung cancers?

Answer 15

K-Ras and p53 (guanine mutations-misread as thymine)

Question 16

what is the active carcinogen in tobacco smoke?

Answer 16

3,4-benzpyrene (benzopyrene)

Question 17

what is the role of AHH in cancer?

Answer 17

converts benzopyrene into benzopyrene diol epoxide which binds to DNA forming damaging products

Question 18

which protein can detoxify carcinogens?

Answer 18

GSTM1 (glutathione S transferase)

Question 19

smoking increases the risk of which other cancers?

Answer 19

+ oesophagus
+ bladder
+ kidney
+ pancreas

Question 20

describe the sources of carcinogens in diet (NITRITES AND NITRATES)?

Answer 20

+ in food additives and fertilisers that enter drinking water

+ gut bacteria converts nitrites and nitrates

+ nitrosamines produced - carcinogens that can lead to GI tract and liver cancers

Question 21

what cancer are aflatoxins (aflatoxin B1) associated with?

Answer 21

liver carcinomas

Question 22

why are there much higher incidences of tumours in large intestine than small intestine?

Answer 22

+ Bcl2 expresses in colonic epithelium

+ Bcl2 not expressed in small intestine

+ Bcl2 suppresses apoptosis therefore damaged cells survive, mutate and lead to carcinogenesis

Question 23

what type of UV radiation causes carcinogenesis?

Answer 23

non-ionising (causes excitation of atoms)

Question 24

which individuals are particularly at risk of UV-induced damage?

Answer 24

repair deficient individuals: xeroderma pigmentosum - rare autosomal recessive disease

Question 25

what is xeroderma pigmentosum?

Answer 25

+ inherited deficiency of endonuclease (enzyme in pathway of thymine dimer removal)

+ children show severe skin abnormalities (freckling, multiple squamous and basal cell carcinomas and melanomas)

+ requires protection from sunlight

Question 26

what types of cancer is associated with ionising radiation?

Answer 26

+ skin (x-ray)
+ leukaemia (thermal and ionising)
+ bone (radium)