title: Inhibition of UVB-induced skin tumor development by drinking green tea polyphenols is mediated through DNA repair and subsequent inhibition of inflammation.
abstract: Consumption of green tea polyphenols (GTPs) in drinking water prevents photocarcinogenesis in mice; however, the molecular mechanisms underlying this effect have not been fully elucidated. Using IL-12p40 knockout (KO) mice and their wild-type counterparts and an established photocarcinogenesis protocol, we found that although administration of GTPs (0.2%, w/v) in drinking water significantly reduced UVB-induced tumor development in wild-type mice, this treatment had a nonsignificant effect in IL-12-KO mice. GTPs resulted in reduction in the levels of markers of inflammation (cyclooxygenase-2, prostaglandin E(2), proliferating cell nuclear antigen, and cyclin D1) and proinflammatory cytokines (tumor necrosis factor-alpha, IL-6, and IL-1beta) in chronically UVB-exposed skin and skin tumors of wild-type mice but less effective in IL-12p40-KO mice. UVB-induced DNA damage (cyclobutane pyrimidine dimers) was resolved rapidly in GTPs-treated wild-type mice than untreated wild-type mice and this resolution followed the same time course as the GTPs-induced reduction in the levels of inflammatory responses. This effect of GTPs was less pronounced in IL-12-KO mice. The above results were confirmed by treatment of IL-12-KO mice with murine recombinant IL-12 and treatment of wild-type mice with neutralizing anti-IL-12 antibody. To our knowledge, it is previously unreported that prevention of photocarcinogenesis by GTPs is mediated through IL-12-dependent DNA repair and a subsequent reduction in skin inflammation.
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Syed M
authors.initials: SM
authors.lastname: Meeran
authors.forename: Suhail
authors.initials: S
authors.lastname: Akhtar
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Katiyar
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001628:Beverages; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004260:DNA Repair / Q000502:physiology* / Q000528:radiation effects; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D010636:Phenols / Q000008:administration & dosage / Q000627:therapeutic use*; D010936:Plant Extracts / Q000008:administration & dosage / Q000627:therapeutic use; D059808:Polyphenols; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012878:Skin Neoplasms / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D018809:Proliferating Cell Nuclear Antigen; D019938:Cyclin D1; D018664:Interleukin-12; D051546:Cyclooxygenase 2; D015232:Dinoprostone