PPT 4 Flashcards
(20 cards)
Best defense against cancer
DNA stability
Tissues minimize accumulations of mutations by
- Small stem cell compartment
- Snelle regeneration of tissues
- Symmetic & assymetic stem cel division
Transit-amplifying cell (TACs)
2nd daughter cell of stem cell
undifferentiated population in transition between stem cells and differentiated cells
symmetic division
Van 1 stam cell -> 2 stam cellen
- growth of organ, increases number of stem cells
Assymmetric divison
van 1 stam cell -> 1 stam cel + 1 transit-amplifying cell
- maintenance of organ size, constant number of stem cells
Targets for oncogenic transormations
- Stem cells (permanently present in tissues)
- Transit-amplifying cells (hoger aantal dan SC, actively dividing
Protective mechanisms
- Apoptosis
- Drug pumps
- Assymmetic DNA replication
> (proofreading)
Barriers for mutagenesis
- DNA replication
- Mismatch repair (MMR)
- Double-strand break (DSB) repair
Source mutagenesis
- Endogenous (Depurination, deprimidination, deamintion, Oxidation by ROS, reactive oxygen species, base mispairing)
- Exogenous (Ionizing radiation, UV, alkylating agents, cellular processes, alcohol)
Cell protects DNA by
- Physical shielding (melanine)
- Reactive oxygen species (ROS) scavengers (Vitamine C, bilirubin, urate) react with ROS
- Enzymes (Glutamthionine S-transferase (GSTs) inactivate electrophilic compounds by linking them with glutathionine
DNA repair proteins
- Base-excision repair (BER)
- Nucleotide excision repair (NER)
(defects cause cancer)
Double strand break repair
- Homologous recombination (HR)
Active in S en G2 phase - Non-homologous end joining (NHEJ)
mostly active in G2
Changes in chromosome structure
- Deletions
- Amplifications
- Translocations
> can lead to loss of heterogeneity (LOH) = loss of 1/1+ alleles of a specific gene
Chromosome Aberrations
changes in structure or number of chromsomes
Chromothripsis
localized, massive chromosome fragmentation, followed by multiple rejoining between resulting fragments.
Changes in chromsome number
- Polyploidy
- Aneuploidy
- Chromosome instability
- Transformation
- Mitotic missegragation
- Nondisjunction of sister chromatids
- Merotly
Genetic instability in cancer
- Allows cancer cells to accumulate genomic changes that are necessary for transformation.
- Dysfunction of repair mechanisms makes cancer cells generally vulnerable, also to treatments that target their DNA
Polyploidy
duplicatie van alle chromosome. mistakes in mitose
Aneuploidy
changes in number of an individual chromosome. Can be caused by mitotic errors or errors in DSB repair
Chromosome instability
a state of susceptibility to change in chromosome number.
