31 - Environmental Basis of Cancer Flashcards

Question

How can the type of initiator be inferred in BCC and SqCC?

Answer 1

The type of initiator can be inferred by the type of mutation found. I.e. P53

Answer 2

- C to T transitions especially in dipyridine sequences | - CC to TT tandem mutations rare in any other cancer

Answer 3

TSG - restrains abnormal growth Often mutated in skin cancers The types of mutations in P53 give an indication of what the carcinogen is

Answer 4

C > T esp at dipyridimine sites | CC > TT (rare)

Answer 5

- UV light breaks the double bond in adjacent cytosines/pyrimidines and links them by a cyclobutane bond to form a cyclobutane ring - if this isn't repaired and the cell replicates then polymerase n guesses and buts 2 As opposite the joined C's - in the successive replication 2 Ts replace the 2 Cs - this mutation is definitive for UV as a carcinogen

Answer 6

- UVB damages DNA - cells die by apoptosis by p53 - if p53 is mutated (C>T) becomes a heterozygote with 1 damaged allele - apoptosis not as efficient in subsequent burns in the heterozygote p53 cells - relative survival and expansion of mutant cells - with every subsequent UV exposure the mutant p53 expand/die less efficiently - form actinic keratoses (dry patches of macroscopic dysplasia) - next UV dose is then likely to cause the loss of the remaining p53 allele - loses control (loss of apoptosis regulation) and becomes a malignant cell

Answer 7

Doesn't cause sunburn but acts as a promoter

Answer 8

``` efficient apoptosis (peeling sunburn) reduced p53 mediated apoptosis expanding mutants loss of apop > malignant change ```

Answer 9

tobacco most important preventable casue of morbidity and mortality (30% of cancers and 90% of lung cancers) CVD biggest killer from tobacco

Answer 10

60 | PAH especially

Answer 11

- in any partially combusted plant material

Answer 12

G>T (C>T in skin cancer) Also acts as a promoter as binds AhR

Answer 13

- Carcinogen | - G > A and binds BAR (adrenaline rececptor) and nAChR

Answer 14

no but it can be transformed at high T into NNK (carcinogen) | Break down product

Answer 15

- tobacco is cured a bond in nicotine breaks and there is an addition to the N atom to form NNK - the body recognises NNK as foreign and hydroxylates the alpha carbon it to solubilise and get rid of it - spontaneously breaks down and methydiazohydorxide is released - methyldiazohydroxide is very reactive - methyl interacts with and binds guanine - methylation of guanine - G - T is now 6OmethylG - T - if not repaired by MGMT becomes 6OmethylG -C - A -T

Answer 16

G > A | UVB is C>T PAH is G > T

Answer 17

methyl guanine dna methyl transferase | High amount of lung cancers with G>A mutation seen in people without this repair enzyme

Answer 18

People who cook over smoking fire (PAH)

Answer 19

- binds AChR and BAR - RAS (oncogene that drives cell signalling) - altered transcriptional activity - new active genes and altered cell phenotypes - proliferation, reduced apoptosis, therapy resistance, MIGRATION

Answer 20

Nitrosaminoketone

Answer 21

- aldehydes (inflam > breakdown of lipids) | - fungal toxin (alfatoxins from Aspergillus flavus)

Answer 22

Alfatoxins from Aspergillus flavus

Answer 23

- alkylates the end G in AGG - (AFB)G-C - A replaces the C - (AFB)G-A - T -A

Answer 24

- initiator is aflatoxin by aspergillus flavus (AGG>AGT) | - promoter is HBV (hep B virus)

Answer 25

- cell death/necrosis - chronic inflam - regeneration/proliferation - proliferation of cells before they repair - DNA damage fixed - proliferation allows outgrowth of mutated cells giving rise to transformed clones

Answer 26

- HBV makes X protein - inhibits repair - binds P53 and indirectly activates RAs protein contributing to outgrowth of abnormal cells

Answer 27

CHRONIC INFLAMMATION makes ROS > scramble DNA and make alkylaters out of lipids Also produces ROS that affect signalling pathways Cytokines act as inducers of epithelial proliferation (repair)