title: Can transcriptomics provide insight into the chemopreventive mechanisms of complex mixtures of phytochemicals in humans?
abstract: Blueberries contain relatively large amounts of different phytochemicals, which are suggested to have chemopreventive properties, but little information is available on the underlying molecular modes of action. This study investigates whole genome gene expression changes in lymphocytes of 143 humans after a 4-week blueberry-apple juice dietary intervention. Differentially expressed genes and genes correlating with the extent of antioxidant protection were identified in four subgroups. The magnitude of the preventive effect after the intervention differed between these four subgroups. Furthermore, subjects in two groups carried genetic polymorphisms that were previously found to influence the chemopreventive response. Pathway analysis of the identified genes showed strong but complex gene expression changes in pathways signaling for apoptosis, immune response, cell adhesion, and lipid metabolism. These pathways indicate increased apoptosis, upgraded growth control, induced immunity, reduced platelet aggregation and activation, blood glucose homeostasis, and regulation of fatty acid metabolism. Based on these observations, we hypothesize that combining transcriptomic data with phenotypic markers of oxidative stress may provide insight into the relevant cellular processes and genetic pathways, which contribute to the antioxidant response of complex mixtures of phytochemicals, such as found in blueberry-apple juice.
authors: 1 Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University , Maastricht, The Netherlands .
authors: Simone G J
authors: SG
authors: van Breda
authors: Lonneke C
authors: LC
authors: Wilms
authors: Stan
authors: S
authors: Gaj
authors: Danyel G J
authors: DG
authors: Jennen
authors: Jacob J
authors: JJ
authors: Briedé
authors: Johannes P
authors: JP
authors: Helsper
authors: Jos C S
authors: JC
authors: Kleinjans
authors: Theo M C M
authors: TM
authors: de Kok
mesh_terms: D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001628:Beverages; D029798:Blueberry Plants / Q000737:chemistry*; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015894:Genome, Human / Q000187:drug effects / Q000235:genetics; D064368:Healthy Volunteers; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D027845:Malus / Q000737:chemistry*; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D010641:Phenotype; D064209:Phytochemicals / Q000737:chemistry / Q000494:pharmacology*; D059467:Transcriptome / Q000187:drug effects* / Q000235:genetics*; D055815:Young Adult
chemical_list: D000975:Antioxidants; D064209:Phytochemicals