title: Cytotoxic effect of linear alkylbenzene sulfonate on human intestinal Caco-2 cells: associated biomarkers for risk assessment.
abstract: Linear alkylbenzene sulfonate (LAS) is a synthetic anionic surfactant widely present in the environment due to its intensive production and use in the detergency field. Admitting that current procedure of risk assessment has limits in providing realistic risk assessment data and predicting the cumulative effect of the toxicant mixtures, the incorporation of information regarding the mode of action and cell response mechanism seems to be a potential solution to overcome these limits. In this regard, we investigated in this study the LAS cytotoxicity on human intestinal Caco-2 cells, trying to unveil the protein actors implicated in the cell response using proteomics approach in order to give a better understanding of the toxicological effect and allow the identification of appropriate biomarkers reflecting the mode of action associated with LAS. As results, we demonstrated that LAS induces a time- and dose-dependent cytotoxicity in Caco-2 cells accompanied by an induction of oxidative stress followed by an excessive increase of intracellular calcium level. Proteomics approach helped in discovering three informative biomarkers of effect associated with LAS cytotoxic effect, reported for the first time: calreticulin, thioredoxin, and heat shock cognate 71 (HSP7C), confirmed by real-time PCR and western blot analysis. These biomarkers could serve for more reliable future risk assessment studies that consider the toxicants mode of action in order to help in the prediction of potential cumulative effects of environmentally coexisting contaminants.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305-8572, Japan.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bradai
authors.forename: Junkyu
authors.initials: J
authors.lastname: Han
authors.forename: Abdelfatteh
authors.initials: A
authors.lastname: El Omri
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Funamizu
authors.forename: Sami
authors.initials: S
authors.lastname: Sayadi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Isoda
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D018938:Caco-2 Cells; D037282:Calreticulin / Q000378:metabolism; D003603:Cytotoxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D040901:Proteomics / Q000379:methods; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment / Q000379:methods; D013501:Surface-Active Agents / Q000633:toxicity*; D013879:Thioredoxins / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D017738:Alkanesulfonic Acids; D015415:Biomarkers; D037282:Calreticulin; D003603:Cytotoxins; D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D013501:Surface-Active Agents; D014874:Water Pollutants, Chemical; C030641:alkylbenzyl sulfonic acid; D013879:Thioredoxins