Thimerosal Induces Apoptosis and G2/M Phase Arrest in Human Leukemia Cells

Abstract

Thimerosal is an organomercury compo und with su lfhydryl-reactive p roperties. The abili ty of thime rosal to act as a sulfhydryl group is related to the presence of mercury. D ue to its antibacterial effect, thimerosal is widely used a s preservatives and has been rep orte d to cause chemicall y medi ated side effects. In the present s tudy, we sh owed that the molecular mechanism of thimero sal induced apoptosi s in U937 cells. Thimerosal was sho wn to be responsible for the i nhibition of U 937 cells growth by induc ing apopt os is. Treatment with 2. 5–5 mM thi merosal but not th iosalicylic acid (structural analog of thim erosal dev oid o f mercury) for 1 2 h produce d apoptos is, G 2 /M phase ar rest, and DNA fragmen tation in a dose-dependent manner. Treatment with caspase in hibitor si gnificantly reduced thi merosal- induced caspase 3 a ctivation. In addition, th im erosa l-induced apoptosis was attenuat ed by antioxidant Mn (III) meso- te traki s (4 -benzoic acid) porphyrin (Mn-TBA P). Thes e dat a indicate that the cy totoxic effect of thimerosal on U937 cells is attributable to the induced apopt os is and that thimerosal-induced apop tosis is mediated by rea ctive o xygen species generation and caspase-3 ac ti vation. ß 2006 Wiley-Liss, Inc. Key words: thimerosa l; apoptosis; ROS; cell cycl e; cas pase; U 937 c ells