Key Event Title
|Level of Biological Organization|
Key Event Components
|regulation of cell cycle||cell cycle-related cyclin||disrupted|
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP|
|Histone deacetylase inhibition leading to testicular toxicity||KeyEvent|
|Not Otherwise Specified||Moderate|
Key Event Description
The dysregulation of cell cycle leads to the decreases in cells. The phosphorylation of p21 (CDKN1A; cyclin dependent kinase inhibitor 1A) regulates its function [Moussa, 2015, Child, 2006]. The up-regulation of p21 level in iron-chelated cancer cells was observed [Moussa, 2015].
How It Is Measured or Detected
The percentage of cells at G1, G0, S, and G2/M phases was determined by flow cytometry analysis using DNA content frequency histogram deconvolution software [Li, 2013]. Cell cycle distribution was analyzed by fluorescence-activated cell sorter (FACS) analysis with a Partec PAS-II sorter [Zupkovitz, 2010]. The four cell cycle phases in living cells can be measured with four-color fluorescent proteins using live cell imaging [Bajar, 2016].
Domain of Applicability
The change in the amounts of cells in G1 phase and S phase of cell cycle was detected in mouse HDAC1-/- fibroblast lines (Mus musculus) [Zupkovitz, 2010].
Moussa RS et al. (2015) Differential targeting of the cyclin-dependent kinase inhibitor, p21CIP/WAF1, by chelators with anti-proliferative activity in a range of tumor cell-types. Oncotarget 6:29694-29711
Child ES and Mann DJ. (2006) The intricacies of p21 phosphorylation. Cell Cycle 5:1313-1319
Li Q, Lambrechts MJ, Zhang Q, Liu S, Ge D, Yin R, Xi M and You Z. Glyphosate and AMPA inhibit cancer cell growth through inhibiting intracellular glycine synthesis. Drug Des Devel Ther 2013; 7: 635-643.
Zupkovitz G et al. (2010) The cyclin-dependent kinase inhibitor p21 is a crucial target for histone deacetylase 1 as a regulator of cellular proliferation. Mol Cell Biol 30:1171-1181
Bajar BT et al. (2016) Fluorescent indicators for simultaneous reporting of all four cell cycle phases. Nat Methods 13: 993-996