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Key Event Title
Decrease, Cell proliferation
|Level of Biological Organization|
Key Event Components
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|Uncoupling of OXPHOS leading to growth inhibition (1)||KeyEvent||Allie Always (send email)||Open for comment. Do not cite||Under Development|
|Mitochondrial ATP synthase antagonism leading to growth inhibition (1)||KeyEvent||Brendan Ferreri-Hanberry (send email)||Under development: Not open for comment. Do not cite|
|Mitochondrial complex III antagonism leading to growth inhibition (1)||KeyEvent||Agnes Aggy (send email)||Under development: Not open for comment. Do not cite|
Key Event Description
Decreased cell proliferation describes the outcome of reduced cell division and cell growth. Cell proliferation is considered the main mechanism of tissue and organismal growth (Conlon 1999). Decreased cell proliferation has been associated with abnormal growth-factor signaling and cellular energy depletion (DeBerardinis 2008).
How It Is Measured or Detected
Multiple types of in vitro bioassays can be used to measure this key event:
- ToxCast high-throughput screening bioassays such as “BSK_3C_Proliferation”, “BSK_CASM3C_Proliferation” and “BSK_SAg_Proliferation” can be used to measure cell proliferation status.
- Commercially available methods such as the well-established 5-bromo-2’-deoxyuridine (BrdU) (Raza 1985; Muir 1990) or 5-ethynyl-2’-deoxyuridine (EdU) assay. Both assays measure DNA synthesis in dividing cells to indicate proliferation status.
Domain of Applicability
Taxonomic applicability domain
This key event is in general applicable to all eukaryotes, as most organisms are known to use cell proliferation to achieve growth.
Life stage applicability domain
This key event is in general applicable to all life stages. As cell proliferation not only occurs in developing organisms, but also in adults.
Sex applicability domain
This key event is sex-unspecific, as both genders use the same cell proliferation mechanisms.
Evidence for Perturbation by Stressor
Conlon I, Raff M. 1999. Size control in animal development. Cell 96:235-244. DOI: 10.1016/s0092-8674(00)80563-2.
DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. 2008. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metabolism 7:11-20. DOI: https://doi.org/10.1016/j.cmet.2007.10.002.
Muir D, Varon S, Manthorpe M. 1990. An enzyme-linked immunosorbent assay for bromodeoxyuridine incorporation using fixed microcultures. Analytical Biochemistry 185:377-382. DOI: https://doi.org/10.1016/0003-2697(90)90310-6.
Raza A, Spiridonidis C, Ucar K, Mayers G, Bankert R, Preisler HD. 1985. Double labeling of S-phase murine cells with bromodeoxyuridine and a second DNA-specific probe. Cancer Research 45:2283-2287.