Distribution of SH‐SY5Y human neuroblastoma cells in the cell cycle following exposure to organophosphorus compounds

Abstract

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.

4-Hydroxy TEMPO Attenuates Dichlorvos Induced Microglial Activation and Apoptosis

“…Cyclin A binds to S phase cyclin dependent kinase 2 (Cdk2) and is required for the cell to progress through the S phase . Our results are in agreement with previous reports which showed checkpoint activation by genotoxins like OPs results in either cell cycle arrest and repair of the damage, senescence, or apoptosis. , In addition, a recent report also showed that 4-HT treatment successfully attenuated the docosahexaenoic acid induced cell cycle arrest and apoptosis in human pulmonary artery smooth muscle cells …”

“…52 Our results are in agreement with previous reports which showed checkpoint activation by genotoxins like OPs results in either cell cycle arrest and repair of the damage, senescence, or apoptosis. 53,54 In addition, a recent report also showed that 4-HT treatment successfully attenuated the docosahexaenoic acid induced cell cycle arrest and apoptosis in human pulmonary artery smooth muscle cells. 55 Doherty et al have demonstrated that the incidence of micronuclei increases after exposure to trichlorfon in human lymphoblastoid cells, which suggests that OPs are potentially genotoxic.…”

Dichlorvos‐induced cell cycle arrest and DNA damage repair activation in primary rat microglial cells

“…Cellular checkpoints are signaling pathways evolved in eukaryotes to maintain genomic integrity. Several reports have shown that checkpoint activation by genotoxins such as OPs results in cell cycle arrest and repair of the damage, senescence or apoptosis (Mattiuzzo et al,2006; Carlson and Ehrich,2008). It is reported that dichlorvos showed stronger apoptosis‐inducing ability than chlorpyrifos at lower doses in human natural killer (NK) cells (Li et al,2007).…”

The SH-SY5Y human neuroblastoma cell line, a relevant in vitro cell model for investigating neurotoxicology in human: Focus on organic pollutants

“…Besides its cytotoxic and esterase-inhibitor effects, CPF treatment can also act on neuronal and dopaminergic markers since it can cause a decrease in TH expression, in dopamine (DA) levels [62,85] and in TUBB3 expression [85] but does not affect glutamic acid decarboxylase 65-kilodalton isoform (GAD65) protein expression which is a marker of GABAergic signaling [62]. Parathion and paraoxon alter the cell cycle status and have effects on f-actin, that may be related to alterations on neurite extension and secretion of neurotransmitters [116,117].…”