Wk 11: Causes of cancer - Smoking (chemistry) Flashcards
What is benzopyrene?
- Carcinogen
- Formed from incomplete combustion of fossil fuels
Where are polycyclic aromatics found?
Soot, tar, car exhaust + burnt food
What is the shape of benzopyrene?
Planar - intercalate into DNA
What happens when CYP is oxidised/hydrolysed in benzopyrene?
Produces epoxides
What are epoxides?
Strong electrophiles due to electronegative oxygen atom + strained 3 membered ring system, nucleophilic DNA react with
What are DNA adducts?
- Cause distortions
- DNA replication disrupted w/ errors from mis-reads, deletions or insertions
What are nitrosoamines known to contribute to?
Lung + bladder cancer
What happens to N-nitrosodimethyl amine when it is activated?
- Turns into potent alkylating agent
- Methyl diazonium ion reacts w/ DNA bases to produce DNA adducts
What adducts do methyl diazonium ions produce when reacting with DNA bases?
- N-7 guanine adduct (major - easily repaired)
- O-6 guanine adduct (minor - not easily repaired)
Which chemotherapy contains methyldiazonium ion?
- Temozolomide
- Dacarbazine
- Streptozotocin
What is acrolein?
Most abundant mutagenic aldehyde in cigs
Which chemical does not need to be metabolically activated to react directly with guanine residues?
Acrolein
What are the signs + symptoms of exposure to acrolein?
- Cough
- SOB
- Headache
- Nausea
What happens when someone is exposed to acrolein when being administered cyclophosphamide + ifosfamide?
Acrolein reactive towards nucleophiles + cysteine residue - causes hemorrhagic cystitis
What are the potential effects of acrolein when inhaled?
Destructive to tissue of mucous membranes + upper respiratory tract
