Forced Uptake of Trivalent and Pentavalent Methylated and Inorganic Arsenic and Its Cyto-/genotoxicity in Fibroblasts and Hepatoma Cells
| Autor: | Ana-Maria Florea, Shweta Yadav, S. Rabieh, Alfred V. Hirner, Elke Dopp, U. von Recklinghausen, Albert W. Rettenmeier, L. M. Hartmann, U. Zimmermann, B. Shokouhi |
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| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Carcinoma
Hepatocellular Cell Survival Metabolite Arsenic biochemistry Chemie chemistry.chemical_element CHO Cells Toxicology medicine.disease_cause Arsenicals Arsenic chemistry.chemical_compound Cricetinae Organometallic Compounds medicine Animals Cacodylic Acid Humans Arsenite Cell Nucleus Micronucleus Tests Dose-Response Relationship Drug integumentary system Arsenic toxicity Cell Cycle Arsenate Fibroblasts Hep G2 Electroporation chemistry Biochemistry Genotoxicity |
| Popis: | Mammals are able to convert inorganic arsenic to mono-, di-, and trimethylated metabolites. In previous studies we have shown that the trivalent organoarsenic compounds are more toxic than their inorganic counterparts and that the toxicity is associated with the cellular uptake of the arsenicals. In the present study, we investigated cyto-/genotoxic effects of the arsenic compounds arsenate [As(i)(V)], arsenite [As(i)(III)], monomethylarsonic acid [MMA(V)], monomethylarsonous acid [MMA(III)], dimethylarsinic acid [DMA(V)], dimethylarsinous acid [DMA(III)], and trimethylarsine oxide [TMAO(V)] after an extended exposure time (24 h) and compared the uptake capabilities of fibroblasts (CHO-9 cells: Chinese hamster ovary) used for genotoxicity studies, with those of hepatic cells (Hep G2: hepatoma cell-line). To find out whether the arsenic compounds are bound to membranes or if they are present in the cytosol, the amount of arsenic was measured in whole-cell extracts and in membrane-removed cell extracts by inductively coupled plasma-mass spectrometry (ICP-MS). In addition, we forced the cellular uptake of the arsenic compounds into CHO-9 cells by electroporation and measured the intracellular arsenic concentrations before and after this procedure. Our results show that organic and inorganic arsenicals are taken up to a higher degree by fibroblasts compared to hepatoma cells. The arsenic metabolite DMA(III) was the most membrane permeable species in both cell lines and induced strong genotoxic effects in CHO-9 cells after an exposure time of 24 h. The uptake of all other arsenic species was relatively low ( |
| Databáze: | OpenAIRE |
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