Int. J. Mol. Sci. 2002, 3(11), 1117-1132; doi:10.3390/i3111117
Article

Differential Cytotoxicity and Gene Expression in Human Liver Carcinoma (HepG2) Cells Exposed to Arsenic Trioxide, and Monosodium Acid Methanearsonate (MSMA)

1 Molecular Toxicology Research Laboratory, NIH-Center for Environmental Health, School of Science and Technology, Jackson State University, 1400 Lynch Street, P.O. Box 18540, Jackson, Mississippi 39217, USA 2 Department of Environmental Health Sciences, Tulane University School of Public Health and Tropical Medicine, 1440 Canal Street, New Orleans, Louisiana 70112, USA
* Author to whom correspondence should be addressed.
Received: 7 June 2002; Accepted: 30 October 2002 / Published: 30 November 2002
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Abstract: Research in our laboratory has demonstrated that a trivalent form of arsenic such as arsenic trioxide (AT) has the ability to cause significant cytotoxicity, and induction of a significant number of stress genes in human liver carcinoma cells (HepG2). However, the literature also indicates that the toxicity of arsenic depends on its chemical form. To test this hypothesis, we further evaluated the cellular and molecular responses of HepG2 cells following exposure to monosodium acid methanearsonate (MSMA), a pentavalent and organic form of arsenic. Cytotoxicity was evaluated using the MTT-assay for cell viability, while the gene profile assay was performed to measure the degree of gene induction in 13 different recombinant cell lines generated from a parental HepG2 cell line. Cytotoxicity experiments yielded LC50 values of 11.9 + 2.6 μg/mL for AT, and 257.3 + 51.4μg/mL for MSMA; indicating that AT was about 20 times more toxic than MSMA. Exposure of HepG2 cells to MSMA also resulted in a significant reduction (p < 0.05) in the number of stress genes induced, compared to AT. Upon MSMA exposure, only 2 (HMTIIA and HSP70) out of the 13 constructs evaluated yielded inductions to statistically significant levels (p < 0.05), compared to 11 (GSTYa, XRE, HMTIIA, c-fos, NF-kBRE, HSP70, p53RE, GADD153, GADD45, and GRP78) for AT. These results greatly support the hypothesis that the toxicity of arsenic compounds highly depends on their chemical forms; with the inorganic forms being more potent than the organic ones.
Keywords: Arsenic; chemical species; differential toxicity; gene expression; HepG2 cells

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MDPI and ACS Style

Tchounwou, P.B.; Wilson, B.A.; Abdelghani, A.A.; Ishaque, A.B.; Patlolla, A.K. Differential Cytotoxicity and Gene Expression in Human Liver Carcinoma (HepG2) Cells Exposed to Arsenic Trioxide, and Monosodium Acid Methanearsonate (MSMA). Int. J. Mol. Sci. 2002, 3, 1117-1132.

AMA Style

Tchounwou PB, Wilson BA, Abdelghani AA, Ishaque AB, Patlolla AK. Differential Cytotoxicity and Gene Expression in Human Liver Carcinoma (HepG2) Cells Exposed to Arsenic Trioxide, and Monosodium Acid Methanearsonate (MSMA). International Journal of Molecular Sciences. 2002; 3(11):1117-1132.

Chicago/Turabian Style

Tchounwou, P. B.; Wilson, B. A.; Abdelghani, A. A.; Ishaque, A. B.; Patlolla, A. K. 2002. "Differential Cytotoxicity and Gene Expression in Human Liver Carcinoma (HepG2) Cells Exposed to Arsenic Trioxide, and Monosodium Acid Methanearsonate (MSMA)." Int. J. Mol. Sci. 3, no. 11: 1117-1132.

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