title: Effect of phytochemicals on phase II enzyme expression in infant human primary skin fibroblast cells.
abstract: Phase II metabolising enzymes enable the metabolism and excretion of potentially harmful substances in adults, but to date it is unclear whether dietary phytochemicals can induce phase II enzymes differently between adults and infants. We investigated the expression of phase II enzymes in an in vitro model of primary skin fibroblasts at three different developmental stages, 1 month, 2 years and adult, to examine potential differences in age-related phase II enzymes in response to different phytochemicals (5-20 μm) including sulphoraphane, quercetin and catechin. Following phytochemical treatment, a significant increase in mRNA of glutathione S-transferase A1 (GSTA1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) was observed, with the most marked increases seen in response to sulphoraphane (3-10-fold for GSTA1, P = 0·001, and 6-35-fold for NQO1, P = 0·001-0·017). Catechin also induced 3-5-fold changes in NQO1 transcription, whereas quercetin had less effect on NQO1 mRNA induction in infant cells. Moreover, NQO1 protein levels were significantly increased in 2-year-old and adult cell models in response to sulphoraphane treatment. These results suggest that metabolic plasticity and response to xenobiotics may be different in infants and adults; and therefore the inclusion of phytochemicals in the infant diet may modulate their induction of phase II metabolism, thereby providing increased protection from potentially harmful xenobiotics in later life.
authors.affiliation: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich              NR4 7TJ, UK.
authors.forename: Eliz
authors.initials: E
authors.lastname: Warwick
authors.forename: Aedín
authors.initials: A
authors.lastname: Cassidy
authors.forename: Bryan
authors.initials: B
authors.lastname: Hanley
authors.forename: Zeina E
authors.initials: ZE
authors.lastname: Jouni
authors.forename: Yongping
authors.initials: Y
authors.lastname: Bao
mesh_terms: D000328:Adult; D002392:Catechin / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000201:enzymology; D015870:Gene Expression / Q000187:drug effects*; D005982:Glutathione Transferase / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics*; D017879:Isothiocyanates; D050217:Metabolic Detoxication, Phase II; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000032:analysis / Q000235:genetics*; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
chemical_list: D007527:Isoenzymes; D017879:Isothiocyanates; D012333:RNA, Messenger; D013454:Sulfoxides; D013861:Thiocyanates; D002392:Catechin; D011794:Quercetin; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha; C016766:sulforaphane