title: Singlet oxygen mediated apoptosis by anthrone involving lysosomes and mitochondria at ambient UV exposure.
abstract: Anthrone a tricyclic aromatic hydrocarbon which is toxic environmental pollutant comes in the environment through photooxidation of anthracene. We have studied the photomodification of anthrone under environmental conditions. Anthrone generates reactive oxygen species (ROS) like (1)O2 through Type-II photodynamic reaction. Significant intracellular ROS generation was measured through dichlorohydrofluorescein fluorescence intensity. The generation of (1)O2 was further substantiated by using specific quencher like sodium azide. UV induced photodegradation of 2-deoxyguanosine and photoperoxidation of linoleic acid accorded the involvement of (1)O2 in the manifestation of anthrone phototoxicity. Phototoxicity of anthrone was done on human keratinocytes (HaCaT) through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and neutral red uptake assays. Anthrone induced cell cycle arrest (G2/M-phase) and DNA damage in a concentration dependent manner. We found apoptosis as a pattern of cell death which was confirmed through sub-G1 fraction, morphological changes, caspase-3 activation, acridine orange/ethidium bromide staining and phosphatidylserine translocation. Mitochondrial depolarization and lysosomal destabilization was parallel to apoptotic process. Our RT-PCR results strongly supports our view point of apoptotic cell death through up-regulation of pro-apoptotic genes p21 and Bax, and down regulation of anti-apoptotic gene Bcl2. Therefore, much attention should be paid to concomitant exposure of anthrone and UV-R for its total environmental impact.
authors.affiliation: Photobiology Division, CSIR, Indian Institute of Toxicology Research, Post Box No 80, MG Marg, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Syed Faiz
authors.initials: SF
authors.lastname: Mujtaba
authors.forename: Ashish
authors.initials: A
authors.lastname: Dwivedi
authors.forename: Neera
authors.initials: N
authors.lastname: Yadav
authors.forename: R S
authors.initials: RS
authors.lastname: Ray
authors.forename: Gajendra
authors.initials: G
authors.lastname: Singh
mesh_terms: D000873:Anthracenes / Q000528:radiation effects* / Q000633:toxicity*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004249:DNA Damage; D004785:Environmental Pollutants / Q000528:radiation effects* / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019787:Linoleic Acid / Q000737:chemistry / Q000528:radiation effects; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D026082:Singlet Oxygen / Q000737:chemistry; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein / Q000235:genetics; D000095322:Anthrones
chemical_list: D000873:Anthracenes; D053148:Caspase 3; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004785:Environmental Pollutants; D019787:Linoleic Acid; D010718:Phosphatidylserines; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D026082:Singlet Oxygen; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C493956:CDKN1A protein, human; C004522:anthrone; D000095322:Anthrones