Lecture 31 - Environmental Basis of Cancer

Question 1

Complete Carcinogen?

Answer 1

Able to cause cancer by itself

Question 2

Papilomas?

Answer 2

Premalignant lesions

Question 3

Initiator Promoter relationship?

Answer 3

Initiators must precede, are irreversible i.e. timely gap between will still develop tumour, promotors are reversible as timely gap between promotors wont develop tumor

Question 4

Why is initiation irreversible?

Answer 4

DNA is the target - cause mutations changing gene structure

Question 5

Why are prmotors reversible?

Answer 5

Proteins are the target - alter signalling pathways changing gene expression

Question 6

Wavelengths of UV light?

Answer 6

UVB is short, UVA is long

Question 7

UV light skin penetration?

Answer 7

B weak, A strong

Question 8

UV sunburn?

Answer 8

B strong, A weak

Question 9

UV Targets?

Answer 9

B is DNA, A is skin molecules forming reactive oxygen species

Question 10

UV Carcinogen status?

Answer 10

B is strong complete, A is weak complete

Question 11

3 skin cancers?

Answer 11

Basal cell carcinoma, squamous cell carcinoma, melanoma (rare)

Question 12

Tumor suppressant gene mutation?

Answer 12

C -> T, CC->TT (rare)

Question 13

Mutation process?

Answer 13

UV presence breaks double bond in cytosine and forms cyclobutane ring for neighbouring cytosines; during replication DNA polymerase eta has to guess opposing strand, forms adenosines; further replication forms thymines opposing adenosines

Question 14

Regular UV effecting apoptosis?

Answer 14

DNA mutilation stimulates presence of tumor suppression gene p53 to promote apoptosis

Question 15

UV targeting p53?

Answer 15

knocks one allele, still one left for function, but less efficacy, causing expansion of mutant cells failing to apoptose - actinic keratoses formation

Question 16

UV attacking actinic keratoses?

Answer 16

Eventually mutation will destroy remaining allele, preventing inhibition of malignancy

Question 17

Polycyclic Aromatic Hydrocarbon (PAH) target?

Answer 17

G -> T; AhR

Question 18

NNK targets?

Answer 18

G -> A; beat-adrenergic receptor (bAR), nAchR

Question 19

Tobacco induced mutation?

Answer 19

G-C base pair becomes 60MeG-C, if not repaired, pair divides and 60MeG acts like A and binds to T, if not repaired division binds T to A, mutating G into A

Question 20

Tobacco receptor action?

Answer 20

NNK binds to nAchR or bAR, induces RAS pathway, alters transcriptional activity - increased proliferation, suppress apoptosis, effect migration

Question 21

Chronic inflammation leading to cancer?

Answer 21

Produces reactive oxygen species that: produce alkalators out of lipids and produce reactive oxygen species that affect signalling pathways as well s cytokines that promote cell proliferation