title: Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells.
abstract: BACKGROUND
  Arsenic is a ubiquitous environmental toxicant, and abnormalities of the skin, lung, kidney, and liver are the most common outcomes of long-term arsenic exposure. This study was designed to investigate the possible mechanisms of genotoxicity induced by arsenic trioxide in human hepatocellular carcinoma cells.
  
  
  RESULTS
  A mild cytotoxic response of arsenic trioxide was observed in human hepatocellular carcinoma cells, as evident by (3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) and lactate dehydrogenase assays after 24 and 48 hours of exposure. Arsenic trioxide elicited a significant (P < 0.01) reduction in glutathione (15.67% and 26.52%), with a concomitant increase in malondialdehyde level (67.80% and 72.25%; P < 0.01), superoxide dismutase (76.42% and 81.09%; P < 0.01), catalase (73.33% and 76.47%; P < 0.01), and reactive oxygen species generation (44.04% and 56.14%; P < 0.01) after 24 and 48 hours of exposure, respectively. Statistically significant (P < 0.01) induction of DNA damage was observed by the comet assay in cells exposed to arsenic trioxide. It was also observed that apoptosis occurred through activation of caspase-3 and phosphatidylserine externalization in human hepatocellular carcinoma cells exposed to arsenic trioxide.
  
  
  CONCLUSIONS
  The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.
authors: Cell and Molecular Laboratory, Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia;
authors: Saud
authors: S
authors: Alarifi
authors: Daoud
authors: D
authors: Ali
authors: Saad
authors: S
authors: Alkahtani
authors: Maqsood A
authors: MA
authors: Siddiqui
authors: Bahy A
authors: BA
authors: Ali
keywords: DNA damage; apoptosis; arsenic trioxide; hepatocellular carcinoma cells; oxidative stress
references: Oncologist. 2001;6 Suppl 2:22-8
references: 11331437
references: Apoptosis. 2007 May;12(5):913-22
references: 17453160
references: Chemosphere. 2008 May;71(10):1823-31
references: 18359502
references: Anal Biochem. 1976 May 7;72:248-54
references: 942051
references: J Immunol Methods. 1983 Dec 16;65(1-2):55-63
references: 6606682
references: Environ Health Perspect. 1999 Jul;107(7):593-7
references: 10379007
references: Proc Soc Exp Biol Med. 1955 Oct;90(1):210-3
references: 13273400
references: J Appl Toxicol. 2011 Mar;31(2):95-107
references: 21321970
references: Mol Biotechnol. 2004 Mar;26(3):249-61
references: 15004294
references: Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8103-7
references: 9653147
references: Br J Haematol. 2001 Aug;114(2):466-73
references: 11529871
references: J Cell Biochem. 2004 Sep 1;93(1):173-87
references: 15352174
references: Anal Biochem. 1972 Jun;47(2):389-94
references: 4556490
references: Int J Environ Res Public Health. 2004 Sep;1(2):83-9
references: 16696182
references: Clin Cosmet Investig Dermatol. 2011;4:183-90
references: 22253543
references: Nat Rev Cancer. 2002 Jun;2(6):420-30
references: 12189384
references: Free Radic Biol Med. 2002 Sep 15;33(6):864-73
references: 12208374
references: Arch Biochem Biophys. 1959 May;82(1):70-7
references: 13650640
references: Free Radic Biol Med. 1999 Sep;27(5-6):612-6
references: 10490282
references: Regul Pept. 2010 Apr 9;161(1-3):58-66
references: 20093144
references: Mutat Res. 1999 Apr 26;441(1):155-60
references: 10224332
references: Free Radic Biol Med. 2005 May 15;38(10):1311-22
references: 15855049
references: Toxicology. 2011 Jul 29;285(3):142-51
references: 21565247
references: Mol Cell Biochem. 2010 May;338(1-2):225-32
references: 20016928
references: J Invest Dermatol. 2003 Oct;121(4):881-93
references: 14632209
references: Anal Biochem. 1979 Jun;95(2):351-8
references: 36810
references: Hum Hered. 1991;41(1):71-3
references: 2050385
references: J Trace Elem Med Biol. 2008;22(4):262-84
references: 19013355
references: Toxicol In Vitro. 2009 Oct;23(7):1365-71
references: 19699289
references: Mol Cell Biol. 1985 May;5(5):949-56
references: 2987683
references: Mol Toxicol. 1989 Winter;2(1):1-9
references: 2615768
references: Mutat Res. 1994 May 1;307(1):261-71
references: 7513806
references: Mol Cell Biochem. 2007 Jul;301(1-2):123-30
references: 17216127
references: Exp Cell Res. 1988 Mar;175(1):184-91
references: 3345800
references: EMBO J. 1987 Jan;6(1):55-61
references: 3034579
references: N Engl J Med. 1998 Nov 5;339(19):1389-91
references: 9801402
references: Environ Mol Mutagen. 2000;35(3):206-21
references: 10737956
references: Indian J Biochem Biophys. 1984 Apr;21(2):130-2
references: 6490072
references: J Invest Dermatol. 1999 Jul;113(1):26-31
references: 10417614