title: Chemoprevention against arsenic-induced mutagenic DNA breakage and apoptotic liver damage in rat via antioxidant and SOD1 upregulation by green tea (Camellia sinensis) which recovers broken DNA resulted from arsenic-H2O2 related in vitro oxidant stress.
abstract: Green tea (Camellia sinensis; CS) strongly reverses/prevents arsenic-induced apoptotic hepatic degeneration/micronecrosis and mutagenic DNA damage in in vitro oxidant stress model and in rat as shown by comet assay and histoarchitecture (HE and PAS staining) results. Earlier, we demonstrated a link between carcinogenesis and impaired antioxidant system-associated mutagenic DNA damage in arsenic-exposed human. In this study, arsenic-induced (0.6 ppm/100 g body weight/day for 28 days) impairment of cytosolic superoxide-dismutase (SOD1), catalase, xanthine-oxidase, thiol, and urate activities/levels led to increase in tissue levels of damaging malondialdehyde, conjugated dienes, serum necrotic-marker lactate-dehydrogenase, and metabolic inflammatory-marker c-reactive protein suggesting dysregulation at the transcriptional/signal-transduction level. These are decisively restrained by CS-extract (≥10 mg/ml aqueous) with a restoration of DNA/tissue structure. The structural/functional impairment of dialyzed and centrifugally concentrated (6-8 kd cutoff) hepatic SOD1 via its important Cys modifications by H2O2/arsenite redox-stress and that protection by CS/2-mercaptoethanol are shown in in vitro/in situ studies paralleling the present Swiss-Model-generated rSOD1 structural data. Here, arsenite(3+) incubation (≥10(-8) μM + 10 mM H2O2, 2 hr) is shown for the first time with this low-concentration to initiate breakage in rat hepatic-DNA in vitro whereas, arsenite/H2O2/UV-radiation does not affect DNA separately. Arsenic initiates Fe and Cu ion-associated free-radical reaction cascade in vivo. Here, 10 μM of Cu(2+)/Fe(3+)/As(3+) +H2O2-induced in vitro DNA fragmentation is prevented by CS (≥1 mg/ml), greater than the prevention of ascorbate or tocopherol or DMSO or their combination. Moreover, CS incubation for various time with differentially and already degraded DNA resulted from pre-incubation in 10 μM As(3+)-H2O2 system markedly recovers broken DNA. Present results decisively suggest for the first time that CS and its mixed polyphenols have potent SOD1 protecting, diverse radical-scavenging and antimutagenic activities furthering to DNA protection/therapy in arsenic-induced tissue necrosis/apoptosis.
authors.affiliation: a Post Graduate Department of Biochemistry and Biotechnology, Cell and Molecular Therapeutics Laboratory , Oriental Institute of Science and Technology, Vidyasagar University , Midnapore , West Bengal , India.
authors.forename: Nirmallya
authors.initials: N
authors.lastname: Acharyya
authors.forename: Sandip
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: Smarajit
authors.initials: S
authors.lastname: Maiti
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D018053:Arsenites / Q000633:toxicity*; D002097:C-Reactive Protein / Q000378:metabolism; D028241:Camellia sinensis / Q000737:chemistry*; D020552:Comet Assay; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D053938:DNA Fragmentation / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects; D005260:Female; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009153:Mutagens / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D017208:Rats, Wistar; D017670:Sodium Compounds / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000096:biosynthesis*; D000072105:Superoxide Dismutase-1; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018053:Arsenites; D009153:Mutagens; D010936:Plant Extracts; C000606290:SOD1 protein, human; D017670:Sodium Compounds; C017947:sodium arsenite; D002097:C-Reactive Protein; D006861:Hydrogen Peroxide; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D014969:Xanthine Oxidase
keywords: Camellia sinensis; DNA breakage; arsenic and antioxidant systems; chemoprevention; cytosolic or Cu-Zn SOD (SOD1); green tea; hepatic carcinogenesis