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
/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