title: Analysis of 3-MCPD- and 3-MCPD dipalmitate-induced proteomic changes in rat liver.
abstract: 3-Monochloropropane-1,2-diol (3-MCPD) and 3-MCPD fatty acid esters are process contaminants in foodstuff which are generated during thermal treatment. Long-term exposure to 3-MCPD or 3-MCPD esters causes toxicity especially in kidney and testis. 3-MCPD esters are efficiently hydrolyzed in the gastrointestinal tract, suggesting that their toxicity is mediated by free 3-MCPD. Combined exposure to free 3-MCPD and 3-MCPD released from 3-MCPD esters might lead to dietary consumption above the tolerable daily intake of 2 μg/kg body weight/day. Suspected mechanisms of 3-MCPD toxicity include the inhibition of glycolysis and oxidative stress. Here, a comparative proteomic approach was followed to analyze the effects of 3-MCPD or 3-MCPD dipalmitate in livers from rats exposed to 10 mg/kg body weight 3-MCPD, an equimolar dose of 3-MCPD dipalmitate, or a 4-fold lower dose of the ester during a 28-day repeated-dose feeding study. Early cellular changes were monitored in the absence of overt toxicity. A comprehensive view of 3-MCPD- or 3-MCPD dipalmitate-triggered proteomic changes in rat liver links to previously proposed mechanisms of toxicity and substantially extends our knowledge on molecular hepatic effects of 3-MCPD. Organ-independent marker proteins altered upon 3-MCPD exposure, for example DJ-1/PARK7, were identified by comparison of the proteomic patterns of kidney, testis and liver.
authors.affiliation: Federal Institute for Risk Assessment, Department Food Safety, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany. Electronic address: Albert.Braeuning@bfr.bund.de.
authors.forename: Albert
authors.initials: A
authors.lastname: Braeuning
authors.affiliation: Federal Institute for Risk Assessment, Department Food Safety, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Sawada
authors.affiliation: Federal Institute for Risk Assessment, Department Food Safety, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Oberemm
authors.affiliation: Federal Institute for Risk Assessment, Department Food Safety, Max-Dohrn-Str. 8-10, 10589, Berlin, Germany.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Lampen
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D000517:alpha-Chlorohydrin / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*
chemical_list: D011506:Proteins; D000517:alpha-Chlorohydrin
keywords: 3-Chloro-1,2-monopropanediol; Food carcinogen; Heat-induced process contaminant; Hepatotoxicity