Mechanisms of Cell Death Flashcards
dsDNA break / Gy
40
ssDNA break / Gy
500~1000
base damage / Gy
1000~2000
sugar damage / Gy
800-1600
DNA crosslinks / Gy
30
DNA-protein crosslinks /Gy
150
2 hit hypothesis
1st hit is inherited; second is environmental
Loss of tumor suppressor gene PTEN
glioblastoma
Amplification of N-myc-oncogene
neuroblastoma
Copy number CIN vs. Structural CIN
Chromosomal instability. copy number varies naturally between individuals. Structural leads to cancer.
Base substitution example
P53 in skin cancer
Base deletion example
TGFb RII in colon cancer
microsatellites
short tandem repeats; “junk DNA”
homozygous microsatellite
both strands have same number of repeats
heterozygous microsatellite
each strand has different number of repeats
most sensitve part of cell cycle to radiation
G-2
MRD
minimal residual disease
5 R’s of radiation therapy
- radiosensitivity
- reoxygenation
- repair
- redistribution
- repopulation
Radiosensitivity
intrinsic cellular feature
reoxygenation
hypoxic cells 3x more resistant than anoxic cells
2 forms of cell death
apoptosis
non-apoptotic cell death
apoptosis mechanisms
Extrinsic - death receptor
Intrinsic - mitochondrial
forms of non-apoptotic cell death
- necrosis
- senescence
- autophagy
- mitotic catastrophe
necrosis
passive cell death. unregulated
senescence
living cell death. cell cycle arrest. no reproduction
autophagy
degraded with lysosomes
mitotic catastrophe
aberrant mitosis
