title: Redox-linked effects of green tea on DNA damage and repair, and influence of microsatellite polymorphism in HMOX-1: results of a human intervention trial.
abstract: Green tea has many reported health benefits, including genoprotective and antioxidant effects, but green tea has pro-oxidant activity in vitro. A tea-induced pro-oxidant shift that triggers cytoprotective adaptations has been postulated, but human data are lacking. We investigated effects on oxidation-induced DNA damage and redox-linked cytoprotective factors, including 8-oxoguanine glycosylase (hOGG1) and heme oxygenase 1 (HMOX-1) in lymphocytes in a randomised, placebo-controlled, cross-over supplementation trial. hOGG1 catalyses the first step in base excision repair; increased HMOX-1 is a sign of cytoprotective response to pro-oxidant change. The influence of microsatellite polymorphisms in the HMOX-1 promoter region was also explored. Higher numbers of GT repeats [GT(n)] in this region reportedly diminish response to pro-oxidant change. Green tea [2 × 150 ml of 1% w/v tea/day (or water as control)] was taken for 12 weeks by 43 Type 2 diabetes subjects {20 with short [S/S; GT(n) < 25] and 23 with long [L/L; GT(n) ≥ 25]}. Fasting venous blood was collected before and after each treatment. The formamidopyrimidine DNA glycosylase-assisted comet assay was used to measure DNA damage in lymphocytes. For measuring hOGG1 activity, we used photo-damaged HeLa cells incubated with lymphocyte extracts from test subjects, in combination with the comet assay. Lymphocyte HMOX-1 and hOGG1 protein concentrations and expression (mRNA) of redox-sensitive genes, including HMOX-1 and hOGG1, were also investigated. Results showed significantly (P < 0.01) lower (~15%) DNA damage, higher (~50%) hOGG1 activity and higher (~40%) HMOX-1 protein concentration after tea. No changes in mRNA expression were seen. Baseline HMOX-1 protein and hOGG1 activity were higher (P < 0.05) in the S/S group, but tea-associated responses were similar in both GT(n) groups. Green tea is clearly associated with lowered DNA damage, increased hOGG1 activity and higher HMOX-1 protein levels. Further study is needed to confirm a cause and effect relationship and to establish if these effects are mediated by post-translational changes in proteins or by increased gene expression.
authors.affiliation: Department of Health Technology and Informatics, Hong Kong Polytechnic University, 11 Yuk Choi Rd, Hung Hom, Kowloon, Hong Kong, Centre for Diabetes Education and Management, Our Lady of Maryknoll Hospital, 118 Shatin Pass Road, Wong Tai Sin, Kowloon, Hong Kong and Department of Nutrition, University of Oslo, PO Box 1046, Blindern, 0316 Oslo, Norway.
authors.forename: Siu-Wai
authors.initials: SW
authors.lastname: Choi
authors.affiliation: Centre for Diabetes Education and Management, Our Lady of Maryknoll Hospital, 118 Shatin Pass Road, Wong Tai Sin, Kowloon, Hong Kong and.
authors.forename: Vincent T F
authors.initials: VT
authors.lastname: Yeung
authors.affiliation: Department of Nutrition, University of Oslo, PO Box 1046, Blindern, 0316 Oslo, Norway.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Collins
authors.affiliation: Department of Health Technology and Informatics, Hong Kong Polytechnic University, 11 Yuk Choi Rd, Hung Hom, Kowloon, Hong Kong, Centre for Diabetes Education and Management, Our Lady of Maryknoll Hospital, 118 Shatin Pass Road, Wong Tai Sin, Kowloon, Hong Kong and Department of Nutrition, University of Oslo, PO Box 1046, Blindern, 0316 Oslo, Norway htbenzie@polyu.edu.hk.
authors.forename: Iris F F
authors.initials: IF
authors.lastname: Benzie
mesh_terms: D020552:Comet Assay; D018592:Cross-Over Studies; D019610:Cytoprotection / Q000187:drug effects*; D004249:DNA Damage / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics; D043382:DNA-Formamidopyrimidine Glycosylase; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006367:HeLa Cells; D051547:Heme Oxygenase-1 / Q000235:genetics; D006723:Hong Kong; D006801:Humans; D008214:Lymphocytes; D018895:Microsatellite Repeats / Q000235:genetics; D028321:Plant Preparations / Q000494:pharmacology*; D011110:Polymorphism, Genetic / Q000187:drug effects*; D013662:Tea
chemical_list: D028321:Plant Preparations; D013662:Tea; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D043382:DNA-Formamidopyrimidine Glycosylase