Effect of tris-(2-chloroethyl)-phosphate (TCEP) at environmental concentration on the levels of cell cycle regulatory protein expression in primary cultured rabbit renal proximal tubule cells

Tris-(2-chloroethyl)-phosphate (TCEP) is a typical organophosphate flame retardant and has been designated as a micropollutant in aquatic environment. However, the potential effect of TCEP at environmental concentration is mostly unknown. Thus, the purpose of this study was to investigate the renal effect of TCEP at environmental concentration using primary cultured rabbit renal proximal tubule cells (PTCs). The results showed that TCEP at 10 mgL(-1) decreased cell viability, 84.2% of the control, but increased lactate dehydrogenase, 150% fold of the control. TCEP at 10 mgL(-1) also inhibited expression of CDK4, cyclin D1, CDK2, and cyclin E (79.3%, 77.7%, 73.3%. and 67.8% of the control, respectively), but increased expression of p21(WAF/Cip1) and p27(KiP1) (167.7% and 141.3% of the control, respectively). TCEP decreased DNA synthesis and cell number, 77% and 70% of the control, respectively. Through study of cell viability, cell damage, cell cycle regulator expression, DNA synthesis and cell number, TCEP at 10 mu gL(-1) only affected the cells that TCEP increased expression of P21(WAF/Cip1) and p27(Kip1), 118.6% and 121.5% of the control, respectively, but decreased DNA synthesis, 91.5% of the control. In conclusion, TCEP at 10 mu gL(-1) significantly increased cell cycle regulatory protein expression (p21(WAF/Cip1) and p27(Kip1)), but slightly decreased DNA synthesis in primary cultured rabbit renal PTCs. (c) 2008 Elsevier Ltd. All rights reserved.