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Distribution of SH‐SY5Y human neuroblastoma cells in the cell cycle following exposure to organophosphorus compounds
Author(s) -
Carlson Kent,
Ehrich Marion
Publication year - 2008
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.20229
Subject(s) - sh sy5y , neuroblastoma , chemistry , distribution (mathematics) , cell cycle , cell , biology , cell culture , biochemistry , genetics , mathematics , mathematical analysis
The current study investigated the relationship of the cell cycle phase (as G 0 /G 1 , S, and G 2 /M) and cytotoxicity (as sub‐G 1 DNA) to determine whether alterations in cell replication were associated with organophosphate (OP) compound induced cytotoxicity. Results demonstrated that, overall, OP compound‐‐induced cell cycle changes were variable and depended on the OP compound, exposure concentration, and temporal relationship to cytotoxicity. Noncytotoxic OP compound treatments substantially decreased the percentage of cells in S phase of the cell cycle when compared to controls. A corresponding increase was seen in the percent of cells in G 0 /G 1 phase of the cell cycle. In the precytotoxic interval of exposure , most cytotoxic OP compound treatments substantially decreased the percentage of cells in G 2 /M phase of the cell cycle. Corresponding increases were seen primarily in G 0 /G 1 phase cells. Effects on cells in S stage of the cell cycle varied with the OP compound. In the during cytotoxic interval of exposure , most cytotoxic OP compound treatments substantially increased the percentage of cells in S phase of the cell cycle. A corresponding decrease in the percent of cells in G 0 /G 1 stage of the cell cycle was observed. Furthermore, treatments either increased or decreased the percentage of cells in G 2 /M phase of the cell cycle when compared to controls, with decreases more likely with the most cytotoxic OP compound exposures. Overall, the in vitro data suggest that exposure to OP compounds can alter the cell cycle status of SH‐SY5Y neuroblastoma cells depending on compound, concentration, and interval from initial exposure. Changes in cell cycle, however, did not differentiate between OP compounds that are known for their ability to acutely inhibit acetylcholinesterase versus those inducing type I and type II delayed neurotoxicity. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:187–201, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20229