title: Assessment of the DNA damaging potency and chemopreventive effects towards BaP-induced genotoxicity in human derived cells by Monimiastrum globosum, an endemic Mauritian plant.
abstract: Naturally occurring compounds have protective effects towards mutagens and carcinogens. The leaf extract of Monimiastrum globosum (Bois de Clous), a Mauritian endemic plant from the Myrtaceae family, was studied for its potency to induce DNA damage in human HepG2 hepatoma cells using DNA migration as a biological endpoint in the alkaline single cell gel electrophoresis (SCGE) assay. This was contrasted with the ability to modulate the benzo[a]pyrene (BaP)-dependent DNA damage in human hepatoma cells. M. globosum caused genotoxicity in HepG2 cells at concentrations exceeding 3mg fresh weight (FW) per ml cell culture in the absence of cytotoxicity. Pre-treatment of the cells with 12.2 microg FW/ml to 1.56 mg FW/ml led to a pronounced antigenotoxic effect towards BaP-induced DNA damage. DNA migration (OTM) was reduced by 66%, 81.5% and 74% for 49, 98 and 195 microg FW/ml, respectively. A U-shaped dose-response curve was derived for M. globosum indicating genotoxic effects in high doses and antigenotoxic effects in low doses. M. globosum extract had total phenolics (15 mg/g FW) with flavonoids (aglycones and conjugates: 8 mg/g FW) and proanthocyanidins (3mg/g FW) as major phenolic subclasses. The hydrolysis of conjugated flavonoids yielded the aglycones quercetin (606 microg/g FW) and kaempferol (117.8 microg/g FW) while HPLC-MS/MS analysis of the total extract revealed free flavonoids such as quercetin (19.2 microg/g FW) and myricetin (2.5 microg/g FW). The antioxidant activity of the extract of M. globosum, assessed by the FRAP and TEAC assays yielded values of 275+/-3.82 micromol/g FW and 346+/-4.2 micromol/g FW, respectively.
authors.affiliation: Institute of Indoor and Environmental Toxicology, Faculty of Medicine, Justus-Liebig University of Giessen, Giessen, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Mersch-Sundermann
authors.forename: Theeshan
authors.initials: T
authors.lastname: Bahorun
authors.forename: Thorsten
authors.initials: T
authors.lastname: Stahl
authors.forename: Vidushi S
authors.initials: VS
authors.lastname: Neergheen
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Soobrattee
authors.forename: Robert
authors.initials: R
authors.lastname: Wohlfarth
authors.forename: Rosa
authors.initials: R
authors.lastname: Sobel
authors.forename: Hubertus E
authors.initials: HE
authors.lastname: Brunn
authors.forename: Tim
authors.initials: T
authors.lastname: Schmeiser
authors.forename: Evelyn
authors.initials: E
authors.lastname: Lamy
authors.forename: Okezie I
authors.initials: OI
authors.lastname: Aruoma
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D016587:Antimutagenic Agents; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D020552:Comet Assay; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D027822:Myrtaceae / Q000737:chemistry*; D010084:Oxidation-Reduction; D010636:Phenols / Q000032:analysis; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D044945:Proanthocyanidins / Q000032:analysis; D012313:RNA / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016587:Antimutagenic Agents; D005419:Flavonoids; D009153:Mutagens; D010636:Phenols; D010936:Plant Extracts; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species; D018336:Receptors, Aryl Hydrocarbon; C013221:proanthocyanidin; D001564:Benzo(a)pyrene; D012313:RNA; D000255:Adenosine Triphosphate; D004247:DNA; D019363:Cytochrome P-450 CYP1A1