title: A risk assessment-driven quantitative comparison of gene expression profiles in PBMCs and white adipose tissue of humans and rats after isoflavone supplementation.
abstract: Quantitative insight into species differences in risk assessment is expected to reduce uncertainty and variability related to extrapolation from animals to humans. This paper explores quantification and comparison of gene expression data between tissues and species from intervention studies with isoflavones. Gene expression data from peripheral blood mononuclear cells (PBMCs) and white adipose tissue (WAT) after 8wk isoflavone interventions in postmenopausal women and ovariectomized F344 rats were used. A multivariate model was applied to quantify gene expression effects, which showed 3-5-fold larger effect sizes in rats compared to humans. For estrogen responsive genes, a 5-fold greater effect size was found in rats than in humans. For these genes, intertissue correlations (r = 0.23 in humans, r = 0.22 in rats) and interspecies correlation in WAT (r = 0.31) were statistically significant. Effect sizes, intertissue and interspecies correlations for some groups of genes within energy metabolism, inflammation and cell cycle processes were significant, but weak. Quantification of gene expression data reveals differences between rats and women in effect magnitude after isoflavone supplementation. For risk assessment, quantification of gene expression data and subsequent calculation of intertissue and interspecies correlations within biological pathways will further strengthen knowledge on comparability between tissues and species.
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands. Electronic address: v.van-der-velpen@uea.ac.uk.
authors.forename: Vera
authors.initials: V
authors.lastname: van der Velpen
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: van 't Veer
authors.affiliation: Sub-Department of Toxicology, Wageningen University, Wageningen, The Netherlands.
authors.forename: M Ariful
authors.initials: MA
authors.lastname: Islam
authors.affiliation: Biometris, Wageningen University, Wageningen, The Netherlands.
authors.forename: C J F
authors.initials: CJ
authors.lastname: Ter Braak
authors.affiliation: Sub-Department of Toxicology, Wageningen University, Wageningen, The Netherlands.
authors.forename: F X Rolaf
authors.initials: FX
authors.lastname: van Leeuwen
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Lydia A
authors.initials: LA
authors.lastname: Afman
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands; RIKILT Wageningen UR, Wageningen, The Netherlands.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Hollman
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Evert G
authors.initials: EG
authors.lastname: Schouten
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
authors.forename: Anouk
authors.initials: A
authors.lastname: Geelen
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D011916:Rats, Inbred F344; D018570:Risk Assessment; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D007529:Isoflavones
keywords: Gene expression; Isoflavones; Multivariate model; Quantitative evaluation; Risk assessment; Species and tissue differences