TY - JOUR
T1 - Cytotoxicity of combinations of arsenicals on rat urinary bladder urothelial cells in vitro
AU - Nascimento, Merielen G.
AU - Suzuki, Shugo
AU - Wei, Min
AU - Tiwari, Ashish
AU - Arnold, Lora L.
AU - Lu, Xiufen
AU - Le, X. Chris
AU - Cohen, Samuel M.
N1 - Funding Information:
We gratefully acknowledge Karen Pennington for her technical assistance and Connie Rosales-Winters for assistance in preparation of this manuscript. M.G. Nascimento's studies at the University of Nebraska Medical Center, Omaha, NE were made possible by a fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2005/59817-0), São Paulo, Brazil.
PY - 2008/7/10
Y1 - 2008/7/10
N2 - Based on epidemiological data, chronic exposure to high levels of inorganic arsenic in the drinking water is carcinogenic to the urinary bladder of humans. The highly reactive trivalent organic arsenicals dimethylarsinous acid (DMAIII) and monomethylarsonous acid (MMAIII) are formed during the metabolism of inorganic arsenic in vivo in addition to the corresponding mono-, di- and trimethylated pentavalent arsenicals. The objective of this study was to determine if combining arsenicals was additive or synergistic toward inducing cytotoxicity in a rat urothelial cell line. The MYP3 cell line, an immortalized but not transformed rat urinary bladder epithelial cell line, was seeded into appropriate culture wells. Treatment with the arsenicals was begun 24 h after seeding and continued for 3 days. Combinations of arsenicals used were DMAIII with arsenite, dimethylarsinic acid (DMAV) or trimethylarsine oxide (TMAO). Combinations of concentrations used were the LC50, one-quarter or one-half the LC50 of one arsenical with one-half or one-quarter the LC50 of the other arsenical. To determine if MYP3 cells metabolize arsenicals, cells were treated with arsenate, arsenite and MMAV as described above and the medium was analyzed by HPLC-ICPMS to determine species and quantity of arsenicals present. When cells were treated with one-quarter or one-half the LC50 concentration of both arsenicals, the cytotoxicity was approximately the same as when cells were treated with half the LC50 concentration or the LC50 concentration, respectively, of either arsenical. Treatment with one-quarter the LC50 concentration of one arsenical plus the LC50 concentration of a second arsenical had similar cytotoxicity as treatment with the LC50 concentration of either of the arsenicals. Quantitation and speciation of arsenicals in the cell culture medium showed that MYP3 cells have some reductase activity but the cells do not methylate arsenicals. The effect on the cytotoxicity of arsenicals in combination was additive rather than synergistic toward a rat urothelial cell line.
AB - Based on epidemiological data, chronic exposure to high levels of inorganic arsenic in the drinking water is carcinogenic to the urinary bladder of humans. The highly reactive trivalent organic arsenicals dimethylarsinous acid (DMAIII) and monomethylarsonous acid (MMAIII) are formed during the metabolism of inorganic arsenic in vivo in addition to the corresponding mono-, di- and trimethylated pentavalent arsenicals. The objective of this study was to determine if combining arsenicals was additive or synergistic toward inducing cytotoxicity in a rat urothelial cell line. The MYP3 cell line, an immortalized but not transformed rat urinary bladder epithelial cell line, was seeded into appropriate culture wells. Treatment with the arsenicals was begun 24 h after seeding and continued for 3 days. Combinations of arsenicals used were DMAIII with arsenite, dimethylarsinic acid (DMAV) or trimethylarsine oxide (TMAO). Combinations of concentrations used were the LC50, one-quarter or one-half the LC50 of one arsenical with one-half or one-quarter the LC50 of the other arsenical. To determine if MYP3 cells metabolize arsenicals, cells were treated with arsenate, arsenite and MMAV as described above and the medium was analyzed by HPLC-ICPMS to determine species and quantity of arsenicals present. When cells were treated with one-quarter or one-half the LC50 concentration of both arsenicals, the cytotoxicity was approximately the same as when cells were treated with half the LC50 concentration or the LC50 concentration, respectively, of either arsenical. Treatment with one-quarter the LC50 concentration of one arsenical plus the LC50 concentration of a second arsenical had similar cytotoxicity as treatment with the LC50 concentration of either of the arsenicals. Quantitation and speciation of arsenicals in the cell culture medium showed that MYP3 cells have some reductase activity but the cells do not methylate arsenicals. The effect on the cytotoxicity of arsenicals in combination was additive rather than synergistic toward a rat urothelial cell line.
KW - Arsenite
KW - Dimethylarsinic acid (DMA)
KW - Dimethylarsinous acid (DMA)
KW - Trimethylarsine oxide (TMAO)
KW - Urinary bladder
KW - Urothelial cell cytotoxicity
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U2 - 10.1016/j.tox.2008.04.007
DO - 10.1016/j.tox.2008.04.007
M3 - Article
C2 - 18502017
AN - SCOPUS:44649128519
SN - 0300-483X
VL - 249
SP - 69
EP - 74
JO - Toxicology
JF - Toxicology
IS - 1
ER -