Environmental basis of cancer Flashcards
Human cancer
Skin cancer: most common
Lung cancer: most lethal
Hep B induced Liver cancer: 2nd major carcinogen effecting humans
Molecular Epidemiology
Links the environmental agents which induce the cancer
Relates enviro to cancer, via studying molecular changes
Complete Carcinogen
An agent which alone has the complete capacity to induce cancer
History of the Complete Carcinogen
1775 Percival Pott: High amount of SqCC (squamous cell carcinomas) in boys who went up chimneys
-specific type of skin cancer associated with chimney sweeps
-linked development of this cancer with soot exposure (component causing PAH (Polycyclic Aromatic Hydrocarbons))
PAH= very hydrophobic chicken wire molecules - benzene linked together
= complete carcinogens
If dilute can see synergy between 2x types of agents
Classical Carcinogenic model
Demonstrates synergy between 2x environmental components
Initiator and Promotor
Classical Carcinogenic model Mouse
- I = Initiator (PAH)
Single low (diluted) complete carcinogen
-diluted so much that cannot cause cancer itself - –Multiple doses of P Promotor (phobol esters from plants)
–synergises with promotor class of carcinogens –> - Papillomas
-benign tumours on skin
-most regress - Fully Malignant SqCC
-small number of papillomas the fully progress
Treatment and Cancer Scale
Initial low does of Initiator alone= mouse doesnt develop cancer
Multiple treatments of Promotor alone PPPP
But low dose I + PPPP = papillomas and SqCC appear
=strong evidence between 2x different types of environmental agents
Specificity about order: Initiator has to come first
Relative Duration: Initiator is Irreversible -delivers long term signal to cell. When acted upon much later by promotor can still induce tumours
Promotor effect Reversible : Multiple Promotors must be giving close to one another
Specificity, Duration and Reversibility of Initiator and Promotors
- Specificity about order: Initiator has to come first
- Relative Duration:
a) Initiator is Irreversible -delivers long term signal to cell. When acted upon much later by promotor can still induce tumours
- target DNA
b) Promotor effect Reversible : Multiple Promotors must be giving close to one another
Mechanism of Initiators
PAH (Polycylic Aromatic Hydrocarbons)
Initiators target DNA
I interact with DNA, causing DNA damage, causing mutation which are heritable by all future cells
=explains irreversibility of system
Mechanism of Promotors
(phobol esters from plants)
Promotors target proteins
-enzymes
-receptors
Proteins turn over (can effect a protein, leave for a while. Protein will be broken down and replaced by new protein)
= Reversibility of promotor effect
Promotion is applied continuously if wanting to add carcinogenic stimulus into system
Initiator summary
PAH Permanent duration DNA target 1. induces damage 2. heritable change Result: Mutations (due to changes to DNA) Changes Gene sequence Overall: Initiator mechanism induced potentially carcinogenic damage (pot. cancer causing)
Promotor Summary
Phobol esters (from plants)
Transient duration
Protein target
Signalling pathways altered
Changes Gene expression (same gene expressed in different ways changing the genetic environment of the cell)
Overall: Promotor mechanism selectively causes outgrowth of initiated cells
3x types of Skin cancer
- Basal cell carcinoma
- most common cancer of caucasians - SqCC
- Basal CC rel. more common - Melanoma
- SqCC more common
- hits and kills in younger people
Skin cancer carinogen
UV
- UVB and UVA
- exposed to it all the time
UVB
290-320nm shorter Wavelength Weakly penetrates into skin (good as is more energetic and would cause more damage) Powerful inducer of Sunburn Targets DNA (potent) Potent Complete Caricnogen
UVA
320-400nm longer Wavelength Stronger penetrating - can get down to basal layer Weak inducer of Sunburn Targets Substances in skin, loose energy and produce ROS (reactive O2 species) in skin -low ROS levels: change cell signalling -high ROS levels:mutagenic Weak complete Carcinogen Potent Promotor
Sunscreen
Have a sunscreen that absorbs both UVB and UVA
-if doesn’t absorb UVA think you’re safe, but can get large amount of UVA that can promote damage