Lecture 16 Thursday November 8 2007
Thursday November 8, 2007
Cancer
- somantic cell mutations
- defect in single abnormal cell must be heritable
- agents that cause cancer mutate the DNA
- certain cancers run in families
- people who inherit succeptability to cancer often have
one mutation is not enough
- it is estimated their is 10 to the power of 16 cell division over the course of a human's life
- spontaneous mutations occur 10 to the power of -6 times per cell division
- in a lifetime, every single gene is likely to have undergone mutation about 10 to the power of 10 times
several rare mutations in the lineage of one cell required
- frequency of most types of cancer increase with age
- mutations slowly accumulate until their are enough of them to cause cancer
- animal models confirm that one mutation is not enough
- it is estimated one needs ten or more mutations before a cell becomes cancerous
- tumor progression is gradual
- cancer develop is slow stages from mildly abnormal cells
- cancer with an external cause
- disease does not appear until long after the initial exposure
- the long you are exposed to something that could mutate you dna the more mutations * you will get
- dangerous over productrion of cells
why do you need some many mutations o get cancer?
- redundancy -
- tumor cells encounter new barriers over time
- new mutations needed to over come them
- this causes genetic instability
genetic instability
- cancer cells have dramatically enhanced mutation rates
- defects in ability to repair local DNA damage- accumulate point mutatiion
- or defects…
there must be an optimal level of mutations to cause cancer
- cancerous growth
- defective control of cell death
- cells that normally die don't
- apoptosis - preprogramed cell death
- apoptosis is a normal process
- defective control of cell differentiation
- differentiation normally associated with less mitosis
- this is related to stem cells
stem cells
- cancer thought to be caused by stem cells going crazy
- stem cells replace other cells
- they have a property that when they divide they produce a daughter but maintain the consistence of the original cell which continues to divide
in cancer…
- the tumor can make a copious amount of stem cells
- lining of stomach, and skin are areas that need to be replaced rapidly
many cancer cells escape a built in limit to proliferation
- differentiation
- DNA damage or stress
- Most cells have a finite number of cell divisions
- senescence - old age for a cell - the cell has divided as much as it possibly can
properties that allows cancer cells to grow
- ignores signals that regulate cell proliferation
- avoid cell death by apoptosis
- escape normal limitation to cell proliferation and don't differentiate
- genetically unstable
- escape from home tissues (invasive)
- survive and proliferte in foreign sites (metastasize)
preventable causes of cancer
- Cancer incidence is different in different countries
- Migrant populations tend to adopt pattern of host country
- identifying the environmental factors is difficult
ames test
- salmanella bacteria
- needs histimdine - which is an amino acid
- mix
- bacteria grows
- if mutagen can cause mutations
- big red colonies will emerge
- the compound can change the DNA by producing the ability to synthisize hisdidine
carcinogines
- damage DNA directly
- more often become damaging only after being changed to more harmful compounds by metablolic processess
- fungal toxin
aflatoxin
peanuts stored in humid locations
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