BIOL1004 Lecture Notes - Lecture 2: Cytochrome P450, Dna Repair, Pyrimidine Dimer
BIOL1004: Topic 4 – Cancer
Lecture 2 – Environmental Factors that Cause Cancer and Mutations
• Genetic changes caused by the environment
• Carcinogenic chemicals
o Cause DNA damage - leads to mutations
• The longer you are exposed to the carcinogen, the sooner you get cancer (see
notes for graph)
• Anti-cancer drugs are actually carcinogenic as they work via causing damage to
cancerous cell DNA
• Natural products are also capable of causing cancer - some mold on peanuts found
in Africa known to cause liver cancer
• Certain things are metabolized by the body into carcinogens
o Carcinogenic risk due to metabolized chemicals
• Age, sex, nutritional status
• Inherited enzymes my be polymorphic
▪ Cytochrome P-450 proteins in liver
• 10% of Caucasians have highly inducible forms:
• Increasing incidence of lung cancer in smokers
▪ Glutathione-S-transferases (GST)
• 50% of Caucasians have a deletions in this gene
• Higher risk of lung and bladder cancer is exposed to cigarette smoke
o Cause cell proliferation
• Accumulate more damage/mutations
• Radiation
o Reasonably minor contributor to human cancers
o Effect is cumulative
o Long latency
• Takes a while to show effects
o 80% of exposure comes form natural sources
• Ie. Sunlight
o UV radiation
• Causes pyrimidine dimers
▪ Also DNA-protein cross links, single strand breaks
▪
• Repaired by nucleotides excision repair pathway
• Xeroderma pigmentation
• 2000x greater risk of skin cancer
• Mutation in one of 7 excision repair proteins
• Ionizing radiation
▪ Electromagnetic (X-rays, y-rays)
▪ Pioneers of x-rays -skin cancers
▪ Atomic bombs
• Leukemias after 7 years
• Solid tumors (breast, colon, thyroid, lung) later
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