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

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Author(s)
Kyung Jin WooTae-Jin LeeJae Hoon BaeByeong-Churl JangDae-Kyu SongJae-We ChoSeong-Il SuhJong-Wook ParkTaeg Kyu Kwon
Keimyung Author(s)
Park, Jong WookKwon, Taeg KyuBae, Jae HoonSong, Dae KyuJang, Byeong ChurlCho, Jae WeSuh, Seong Il
Department
Dept. of Immunology (면역학)
Dept. of Physiology (생리학)
Dept. of Molecular Medicine (분자의학)
Dept. of Dermatology (피부과학)
Dept. of Microbiology (미생물학)
Institute for Medical Science (의과학연구소)
Journal Title
Molecular Carcinogenesis
Issued Date
2006
Volume
45
Issue
9
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
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