Causes of cancer Flashcards
lecture 39
effect of tobacco smoking on cancer
estimated to cause 30% of cancer in the UK, even higher if you include passive smoking
3 groups of envrionmental factors
- chemicals
- radiation
- infectious agents
occupational risks in cancer
- historically - scrotal cancer in chimney sweeps, bladder cancer in dye industry workers.
- sex workers - cervix and anal cancer
- construction workers - mesothelioma after asbestos exposure
x rays during pregnancy?
increase risk of leukaemia
most chemical carcinogens…
are pro-carcinogens and need o be activated via metabolic alteration to derive the ultimate carcinogen.
- show tissue specificity and species specificity
what’s the ultiate carcinogen
a highly reactive electrophilic molecule that directly damages DNA.
examples of synthetic chemical carcinogens
- require in vivo activation
1 - polycyclic hydrocarbons - benzpyrene, benzanthracene, methylcholanthrene
2 - aromatic amines and azo dyes - beta napthylamine
reason for bladder cancer in dye industry
many substances used as dyes were aromatic amines derived from aniline and aminobenzene.
2-napthylamine is activated by addition of a hydroxyl in the liver, then rapidly converted to a harmless derivative by addition of a glucuronyl group and excreted in the urine. in man though, the glucuronyl is removed in the bladder and the reactive compound is released. hence bladder cancer.
2 examples of naturally occuring chemical carcinogens
1 - nitrosamines eg dimethylnitrosamine
2 - aflatoxin - derived from the aspergillus flavens
how are nitrosamines formed
interaction of a secondary amine with nitrous acid under acidic conditions. the stomach is such an environment for the interaction of nitrites (food preservatives and in water) and amines (meat, drugs)
issue with aflatoxin
probably the most potent carciogen known to man. natrual contaminant of peanuts infected with A flavens. activated to a highly reactive epoxide by oxidases in the liver. the epoxide binds directly to DNA bases.
how is radiation exposure measured
in greys = the amount of energy absorbed per unit of tissue. 1 grey = 100 rads
action of radiation
produces free radicals and ions as it passes through tissue, these alter structure of bases or cause strand breaks.
why are alpha particles such an issue
they leave dense tracks of ions and radicals so if they pass close to DNA are likely to cause DSBs.
action of UV
photoactivates pyrimidine residues in DNA so they form dimers where 2 thymidines occur sequentially. usually repaired by NER, defective in XP
cancers in smokers, pipe smokers and tobacco chewers
smokers - squamous cell carcinoma of the bronchus
pipe smokers - carcinoma of the tounge
- tobacco chewers - head and neck cancer
ways of identifying carcinogens
- epidemiology
- animal experiments
- in vivo testing
problems with animal experiments using carcinogens
ethical issues, species specificity, organ specificity, stage specificity
primary screen for carcinogens
bacterial and animal cells, to detect mutagens. cheaper and more reproducable. but limited ability to identify those that require metabolic activation.
difficulty with estimating the risk of exposure to an agent
difficult as we need to know how much is needed to cause cancer, at a high dose may things act as carcinogens.
3 types of infectious agent that can cause cancer
1 - parasites
2 - bacteria
3 - viruses
a parasite that can cause cancer
schistosoma haematobium - carcinoma bladder, probably by inducing chronic irritation.
a bacteria that can cause cancer
helicobacter pylori - a cause of some gastric ulcers and a major risk factor for development of gastric carcinoma and gastric lymphoma
viral association with cervical carcinoma
HPV 16 and 18
viral association with hepatocellular carcinoma
HBV and HCV