Print Email Facebook Twitter Transcriptome analysis provides new insights into liver changes induced in the rat upon dietary administration of the food additives butylated hydroxytoluene, curcumin, propyl gallate and thiabendazole Title Transcriptome analysis provides new insights into liver changes induced in the rat upon dietary administration of the food additives butylated hydroxytoluene, curcumin, propyl gallate and thiabendazole Author Stierum, R. Conesa, A. Heijne, W. Ommen, B.v. Junker, K. Scott, M.P. Price, R.J. Meredith, C. Lake, B.G. Groten, J. TNO Kwaliteit van Leven KvL Publication year 2008 Abstract Transcriptomics was performed to gain insight into mechanisms of food additives butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate (PG), and thiabendazole (TB), additives for which interactions in the liver can not be excluded. Additives were administered in diets for 28 days to Sprague-Dawley rats and cDNA microarray experiments were performed on hepatic RNA. BHT induced changes in the expression of 10 genes, including phase I (CYP2B1/2; CYP3A9; CYP2C6) and phase II metabolism (GST μ2). The CYP2B1/2 and GST expression findings were confirmed by real time RT-PCR, western blotting, and increased GST activity towards DCNB. CC altered the expression of 12 genes. Three out of these were related to peroxisomes (phytanoyl-CoA dioxygenase, enoyl-CoA hydratase; CYP4A3). Increased cyanide insensitive palmitoyl-CoA oxidation was observed, suggesting that CC is a weak peroxisome proliferator. TB changed the expression of 12 genes, including CYP1A2. In line, CYP1A2 protein expression was increased. The expression level of five genes, associated with p53 was found to change upon TB treatment, including p53 itself, GADD45α, DN-7, protein kinase C β and serum albumin. These array experiments led to the novel finding that TB is capable of inducing p53 at the protein level, at least at the highest dose levels employed above the current NOAEL. The expression of eight genes changed upon PG administration. This study shows the value of gene expression profiling in food toxicology in terms of generating novel hypotheses on the mechanisms of action of food additives in relation to pathology. © 2008 Elsevier Ltd. All rights reserved. Molecular Sequence Numbers: GENBANK: AA818024, AA818192, AA818350, AA818412, AA818680, AA818833, AA818896, AA818960, AA819087, AA858732, AA858938, AA858966, AA859305, AA875380, AA876052, AA899808, AA899815, AA900472, AA900486, AA924591, AA926032, AA957616, AA963084, AA964507, AA964615, AA964751, AA997188, AA997994, AA999001, AI029442, AI029652, AI044024, AI044091, AI045500, AI059505, AI059951, AI060206, AI070295, AI070587, AI136404; Chemicals / CAS: butylcresol, 128-37-0, 30587-81-6; curcumin, 458-37-7; cyanide, 57-12-5; cytochrome P450 2B1, 330207-10-8; cytochrome P450 2B2, 331462-97-6; cytochrome P450, 9035-51-2; enoyl coenzyme A hydratase, 9027-13-8; gallic acid propyl ester, 121-79-9; glutathione transferase, 50812-37-8; palmitoyl coenzyme A, 1763-10-6; RNA, 63231-63-0; serum albumin, 9048-46-8; tiabendazole, 148-79-8; Aryl Hydrocarbon Hydroxylases, EC 18.104.22.168; Butylated Hydroxytoluene, 128-37-0; Curcumin, 458-37-7; Cytochrome P-450 CYP1A2, EC 22.214.171.124; Cytochrome P-450 CYP2B1, EC 126.96.36.199; DNA, Complementary; Food Additives; Glutathione Transferase, EC 188.8.131.52; Palmitoyl Coenzyme A, 1763-10-6; Propyl Gallate, 121-79-9; steroid 16-beta-hydroxylase, EC 184.108.40.206; Steroid Hydroxylases, EC 1.14.-; Thiabendazole, 148-79-8 Subject NutritionToxicology and Applied PharmacologyButylated hydroxytolueneCurcuminDrug metabolismMixturesp53Peroxisome proliferationPropyl gallateRatThiabendazoleToxicogenomicsbutylcresolcomplementary DNAcurcumincyanidecytochrome P450cytochrome P450 2B1cytochrome P450 2B2cytochrome P450 2C6cytochrome p450 3a9cytochrome p450 4a3enoyl coenzyme A hydrataseenzymegallic acid propyl esterglutathione transferasegrowth arrest and DNA damage inducible protein 45palmitoyl coenzyme Aphytanoyl coenzyme a dioxygenaseprotein kinase C betaprotein p53RNAserum albumintiabendazoletranscriptomeanimal tissuearticlecontrolled studydietDNA microarrayfood poisoninggene expressiongene expression profilinglivermalemetabolismnonhumannucleotide sequenceratreal time polymerase chain reactionWestern blottingAnimalsAryl Hydrocarbon HydroxylasesBody WeightButylated HydroxytolueneCurcuminCytochrome P-450 CYP1A2Cytochrome P-450 CYP2B1Data Interpretation, StatisticalDietDNA, ComplementaryFood AdditivesGene ExpressionGene Expression ProfilingGlutathione TransferaseLiverMaleOrgan SizeOxidation-ReductionPalmitoyl Coenzyme APropyl GallateRatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionSteroid HydroxylasesThiabendazoleRattus To reference this document use: http://resolver.tudelft.nl/uuid:1cbf0fae-5a4d-4a04-8e5b-b96c03f31228 DOI https://doi.org/10.1016/j.fct.2008.04.019 TNO identifier 240926 ISSN 0278-6915 Source Food and Chemical Toxicology, 46 (8), 2616-2628 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.