smoking

Question 1

what may some of the early stages of lung cancer be?

Answer 1

– persistent cough that gets worse over time
– coughing up blood or increased amounts of mucus
– constant chest pain
– shortness of breath, wheezing or hoarseness
– repeated bouts of pneumonia or bronchitis
– swelling of the neck and face
– appetite loss, weight loss and fatigue

Question 2

how is smokers cough caused?

Answer 2

Smoke destroys important cleansing layer in the lungs, which in turn causes a build-up of mucus
– result is “smokers’ cough,” an alternative method that the lungs take in an attempt to cleanse themselves

Question 3

what are the certain mechanisms for neoplasm formation?

Answer 3

mutation- loss, substitution, rearrangement
addition of new genetic material- result of infection viruses
changed gene expression- epigenetic change

Question 4

what are the 3 main components of cigarette smoke?

Answer 4

benzo[a]pyrene
acrolein
n-nitrosodimethyl amine

Question 5

what is benzo[a]pyrene?

Answer 5

it is a polycyclic aromatic hydrocarbon

Question 6

what was the first isolated carcinogen?

Answer 6

benzo[a]pyrene

Question 7

how are polycyclic aromatics formed?

Answer 7

formed by the incomplete combustion of fossil fuels

Question 8

how does the CYP oxidation/ hydrolysis affect benzo[a]pyrene?

Answer 8

they produce epoxides
there is a strong electrophiles due to electronegative oxygen atom and strained 3-membered ring system; nucleophilic DNA can react

Question 9

what effects does DNA adducts have on benzo[a]pyrene?

Answer 9

DNA adducts are bulky
cause local distortions
DNA replication is disrupted with errors caused by mis-reads, deletions,insertions

Question 10

what do nitrosoamines do?

Answer 10

Nitrosoamines from tobacco smoke known to contribute to lung and bladder cancer

Question 11

how is N-nitrosodimethyl amine activated?

Answer 11

Activated in vivo to potent alkylating agent
this is done by hydroxylation and activation by CYP enzymes

Question 12

what adducts are formed from methyl diazonium ion reacting with DNA bases?

Answer 12

– N-7 Guanine adduct
– O-6 Guanine adduct

Question 13

how is the methyldiazomium ion a carcinogen but also a chemotherapeutic agent?

Answer 13

depends on the amount you give
small amount= carcinogen
large amount= therapeutic agent eg temozolamide

Question 14

what is the different between N-7 guanine adduct vs 0-6 guanine adduct?

Answer 14

N-7
- major adduct
easily repaired

O-6 adduct
minor adduct
not easily repaired
which is a major cause of mis-match

Question 15

what is acrolein?

Answer 15

is one of the must abundant, reactive and mutagenic aldehydes in cigarette
smoke
* is found in cigarette smoke at levels up to 1000x higher than those of polycyclic aromatics

Question 16

what can acrolein react directly with?

Answer 16

can react directly with guanine residues of DNA without being metabolically activated to produce DNA adducts

Question 17

what is acrolein active towards?

Answer 17

is very reactive towards nucleophiles, including thiol-containing proteins
– cysteine residues
– a causative factor of haemorrhagic cystitis in cyclophosphamide and ifosamide administration

Question 18

what are the signs and symptoms of exposure to acrolein? what harm could it do?

Answer 18

– material is extremely destructive to tissue of the mucous membranes and upper respiratory tract, eyes, and skin
– cough, shortness of breath, headache, nausea

Question 19

what are the potential health effects of acrolin?

Answer 19

– inhalation: may be fatal if inhaled; material is extremely destructive to
the tissue of the mucous membranes and upper respiratory tract
– skin: toxic if absorbed through skin; causes skin burns
– eyes: causes eye burns
– ingestion: toxic if swallowed; causes burns
– target organs: liver, cardiovascular system, lungs, eyes, kidney

Question 20

what would chronic acrolein toxicity look like?

Answer 20

– Genotoxicityin vitro -human : fibroblast and lymphocyte
– DNA damage

Question 21

why do DNA adducts cause cancer?

Answer 21

During DNA replication the DNA helix is separated by DNA helicase
* A RNA primer can then be added to the separated DNA strand
* Another enzyme, DNA polymerase, adds nucleotides to the template strand
* If a DNA adduct has formed (e.g. N-7 guanine),
DNA polymerase can ‘mis-read’ the sequence
* This may result in a mutation (e.g.guanine
interacting with thymine)
* Accumulation of unrepaired errors can lead to
carcinogenic change

Question 22

what are the consequences of DNA adducts?

Answer 22

Repair
* Apoptosis
* DNA damage

Question 23

what DNA damage can smoking cause?

Answer 23

– altered DNA by replication -> mutation
– altered RNA by transcription
– altered protein synthesis by translation
– proliferation leads to carcinogenesi

Question 24

what is bupropion?

Answer 24

origionally an antidepressant
but can be used to stop smoking

Question 25

how should bupripion be given?

Answer 25

• Over 18 years old only
• Start 1-2 weeks before target stop date, initially 150 mg OD for 6 days then
  150 mg BD.
• Max period of treatment is 7-9 weeks

Question 26

what is varenicline?

Answer 26

Vareniclineis a partial α4β2 nicotinic receptor partial agonist
can be used to stop smoking

Question 27

how should varenicline be taken?

Answer 27

Start 1-2 weeks before target stop date, initially 0.5 mg OD for 3 days, then
increase to 0.5 mg BD for 4 days, then increase to 1 mg BD for 11 weeks