Carcinogenesis

Question 1

what are the main categories of carcinogens.

Answer 1

chemicals
infectious agents
radiation
minerals
Physiological
chronic inflammation

Question 2

what is the target organ for aflatoxin

Answer 2

liver

Question 3

what are the target organs for alcohol

Answer 3

pharynx, larynx, oesophagus and liver.

Question 4

what is the target organ for asbestos

Answer 4

lungs pleura

Question 5

what is the target organ for X-rays

Answer 5

bone marrow (leukaemia

Question 6

what is the target organ for UV light

Answer 6

skin

Question 7

what is the target organ for oestrogen

Answer 7

breast

Question 8

what is the target organ for tobacco smoke

Answer 8

mouth, lung, oesophagus, pancreas, kidney and bladder.

Question 9

what is the target organ for HBV

Answer 9

liver

Question 10

what is the target organs for HPV

Answer 10

Cervix

Question 11

define carcinogen

Answer 11

any agent that significantly increases the risk of developing cancer

Question 12

what are the 2 types of biochemical carcinogens

Answer 12

Initiators- genotoxic

promoter- non genotoxic

Question 13

define a initiator carcinogen

Answer 13

genotoxic i.e. can chemically modify or damage DNA

Question 14

define a promoter carcinogen

Answer 14

non-genotoxic e.g. induce proliferation and DNA replication

Question 15

how many rounds of cell division are required to show a initiator has been successful in modifying DNA which has been fives by DNA polymerase.

Answer 15

2

Question 16

what are the 2 methods of action by which promoters work

Answer 16

Firstly, they can stimulate the two rounds of DNA replication required for mutation fixation
Secondly, they can stimulate clonal expansion of mutated cells, which enables the accumulation of further mutations

Question 17

how many mutations are required to drive cancer cells

Answer 17

2-8.

Question 18

describe the full pathogenesis of initiator and promoters and how they work together to cause cancer

Answer 18

• Genotoxic initiating agent damages DNA
• Promoting agent fixes damage as a mutation and converts normal cell into mutant initiated cell
• Promoting agent stimulates clonal expansion of initiated cell to produce papillomas
• Further rounds of mutations and clonal expansion allows papilloma to progress to carcinoma

Question 19

abnormal methylation of genera promoters leads to epigenetic inactivation of which class of genes

Answer 19

tumour suppressor genes.

CpG islands in promoter sites are methylated then the gene will no longer be expressed.

Question 20

do mutations in oncogenes lead to gain or loss in function

Answer 20

gain

Question 21

do mutations in tumour suppressor genes lead to gain or loss in function

Answer 21

loss

Question 22

the metabolic activation of carcinogens can be from 2 processes, theses include

Answer 22

direct acting-interact directly with DNA.

Pro carcinogen- require enzymatic (metabolic) activation before they react with DNA,

Question 23

examples of direct acting carcinogens include

Answer 23

oxygen radicals, nitrosomines, UV light and ionising radiation

Question 24

examples of pro carcinogens

Answer 24

aromatic amines, polycyclic aromatic hydrocarbons

Question 25

are most carcinogens direct acting or pro carcinogens

Answer 25

procarcinogens

Question 26

what is the function of the enzymes that help metabolically active pro carcinogens.

Answer 26

enzymes normally function in the detoxification and excretion of toxic chemicals.

Question 27

how does the involvement of enzymes that normally function in the detoxification and excretion of toxic chemicals introduce a genetic influence on the extent to which we are sensitive to genotoxic attack by different agents

Answer 27

people who activate a particular chemical more efficiently are more likely to get cancer, while those that excrete the activated chemical less efficiently are also more likely to get cancer

Question 28

does benzopyrene need metabolic activation before it can interact with DNA

Answer 28

Yes

Question 29

where is benzopyrene obtained

Answer 29

combustion of most organic material such as meat, tobacco and fuel,

Question 30

what gene does benzopyrene cause mutations in (tumour suppressor gene) and what cancer is it associated with

Answer 30

TP53 | Lung cancer.

Question 31

how do genetic polymorphisms affect susceptibility to carcinogenic exposure

Answer 31

Genetic polymorphisms in genes encoding metabolic activation, detoxifying, or DNA repair enzymes may confer greater or lesser susceptibility to the effects of carcinogenic exposure

Question 32

what are the main defences against carcinogenic agents

Answer 32

``` dietary antioxidants detoxification mechanisms DNA repair enzymes Apoptotic response to unprepared genetic damage. immune response to abnormal organism ```

Question 33

how many identifies carcinogens are there in tobacco smoke

Answer 33

``` 19 polycyclic aromatic hydrocarbons acrolein nitrosamines radioactive lead and polonium heavy metal- cadmium and chromium. ```

Question 34

the conversion of alcohol to what molecule increases the risk of DNA damage

Answer 34

acetylaldehyde.

Question 35

what hormone levels do alcohol consumption increase which act as promoters

Answer 35

osetrogen and testosterone

Question 36

is alcohol consumption ncreases uptake of carcinogenic chemicals into cells within the upper GI reduces levels of what needed for DNA replication

Answer 36

folate

Question 37

In breast cancer how does oestrogen act as both a promoter and initiator.

Answer 37

Oestrogen binds to transcription factors, which increase proliferation. Oestrogen converts to estradiol, 3-4 quionne which damages DNA

Question 38

does menarche decrease or increase your risk of breast cancer

Answer 38

decrease- less and less oestrogen.

Question 39

what procedure significantly reduced the risk of breast cancer

Answer 39

Oopherectomy

Question 40

how can chronic inflammatory response result in promoters and imitators being activated

Answer 40

DNA damage from release of free radicals by immune cells - initiation Growth factor induced cell division to repair tissue damage - promotion

Question 41

what key cell links tumour cells and inflammatory response

Answer 41

tumour-associated macrophages (TAMs)

Question 42

what activates tumour-associated macrophages (TAMs)

Answer 42

cytokines released by tumour cells

Question 43

what do tumour-associated macrophages (TAMs) produce

Answer 43

tumour necrosis factor-alpha (TNF-α), a cytokine that induces and maintains the inflammatory response. release reactive oxygen and nitrogen species (ROS and RNS) that can act as complete carcinogens, resulting in mutation by damaging DNA and stimulating proliferative through induction of growth factors ROS - can also induce fibroblasts to undergo autophagy, which releases important nutrients that tumour cells can “feed” on