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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