Phenotypic anchoring of arsenic and cadmium toxicity in three hepatic-related cell systems reveals compound- and cell-specific selective up-regulation of stress protein expression: Implications for fingerprint profiling of cytotoxicity

Gottschalg, Elke; Moore, Nicholas E.; Ryan, Abigail K.; Travis, Lucy C.; Waller, R. Corey; Pratt, Steve D.; Atmaca, Mukadder; Kind, Clive; Fry, Jeffrey R.

doi:10.1016/j.cbi.2006.04.003

Cited by 26 publications

(21 citation statements)

References 33 publications

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“…Moreover, arsenicals are known to induce a number of major stress protein families. ROS are known to induce SH-rich proteins metallothionein (MT) which has antioxidative properties [10]. Alteration of nitric…”

Section: Arsenic Toxicitymentioning

confidence: 99%

Metals and apoptosis: Recent developments

Rana

2008

Journal of Trace Elements in Medicine and Biology

332

175

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Section: Arsenic Toxicitymentioning

confidence: 99%

Metals and apoptosis: Recent developments

Rana

2008

Journal of Trace Elements in Medicine and Biology

332

175

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“…In HepG2 cells exposed for 24 h to toxic insult CdCl 2 and NaAsO2 were reported to be of comparable toxicity with IC50 values of 60–70 µM for cytotoxicity. Concentrations of 15 µM CdCl 2 and NaAsO2, 40 µM CdCl 2 and 55 µM NaAsO2, 60 µM CdCl 2 and 70 µM NaAsO 2 were considered as concentrations that elicited minimal (≤5%), mild (20–25%) more severe (approximately 50%) cytotoxicity respectively [21]. Mandon et al optimized the settings for their EGFP expressing stress inducible clones (6 h toxic induction combined with a 12–18 h recovery period) and obtained an IC50 value of 50 µM for CdCl 2 in 96 well format assays, which is consistent with the literature [10].…”

Section: Resultsmentioning

confidence: 99%

Toxicity Assays in Nanodrops Combining Bioassay and Morphometric Endpoints

Lemaire¹,

Mandon²,

Reboud³

et al. 2007

PLoS ONE

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BackgroundImproved chemical hazard management such as REACH policy objective as well as drug ADMETOX prediction, while limiting the extent of animal testing, requires the development of increasingly high throughput as well as highly pertinent in vitro toxicity assays.MethodologyThis report describes a new in vitro method for toxicity testing, combining cell-based assays in nanodrop Cell-on-Chip format with the use of a genetically engineered stress sensitive hepatic cell line. We tested the behavior of a stress inducible fluorescent HepG2 model in which Heat Shock Protein promoters controlled Enhanced-Green Fluorescent Protein expression upon exposure to Cadmium Chloride (CdCl2), Sodium Arsenate (NaAsO2) and Paraquat. In agreement with previous studies based on a micro-well format, we could observe a chemical-specific response, identified through differences in dynamics and amplitude. We especially determined IC50 values for CdCl2 and NaAsO2, in agreement with published data. Individual cell identification via image-based screening allowed us to perform multiparametric analyses.ConclusionsUsing pre/sub lethal cell stress instead of cell mortality, we highlighted the high significance and the superior sensitivity of both stress promoter activation reporting and cell morphology parameters in measuring the cell response to a toxicant. These results demonstrate the first generation of high-throughput and high-content assays, capable of assessing chemical hazards in vitro within the REACH policy framework.

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“…Few studies have focused on the proteomic differences induced by these toxicants [21, 22]. As proteins are the molecules through which a cell enacts change, the differences found in the proteome may better reflect the actual cellular response.…”

Section: Introductionmentioning

confidence: 99%

Proteomic analysis of low dose arsenic and ionizing radiation exposure on keratinocytes

Berglund

Santana

et al. 2009

Proteomics

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Human exposure to arsenic and ionizing radiation occur environmentally at low levels. While the human health effects of arsenic and ionizing radiation have been examined separately, there is little information regarding their combined effects at doses approaching environmental levels. Arsenic toxicity may be affected by concurrent ionizing radiation especially given their known individual carcinogenic actions at higher doses. We found that keratinocytes responded to either low dose arsenic and/or low dose ionizing radiation exposure, resulting in differential proteomic expression based on 2DGE, immunoblotting and statistical analysis. Seven proteins were identified that passed a rigorous statistical screen for differential expression in 2DGE and also passed a strict statistical screen for follow-up immunoblotting. These included: α-enolase, epidermal-fatty acid binding protein, heat shock protein 27, histidine triad nucleotide-binding protein 1, lactate dehydrogenase A, protein disulfide isomerase precursor and S100A9. Four proteins had combined effects that were different than would be expected based on the response to either individual toxicant. These data demonstrate a possible reaction to the combined insult that is substantially different from that of either separate treatment. Several proteins had different responses than what has been seen from high dose exposures, adding to the growing literature suggesting that the cellular responses to low dose exposures are distinct.

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Phenotypic anchoring of arsenic and cadmium toxicity in three hepatic-related cell systems reveals compound- and cell-specific selective up-regulation of stress protein expression: Implications for fingerprint profiling of cytotoxicity

Cited by 26 publications

References 33 publications

Metals and apoptosis: Recent developments

Metals and apoptosis: Recent developments

Toxicity Assays in Nanodrops Combining Bioassay and Morphometric Endpoints

Proteomic analysis of low dose arsenic and ionizing radiation exposure on keratinocytes

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