title: Superoxide mediated photomodification and DNA damage induced apoptosis by Benz(a)anthracene via mitochondrial mediated pathway.
abstract: Benz(a)anthracene (BA) is an ubiquitous environmental pollutant of polycyclic aromatic hydrocarbon's (PAHs) family. We showed superoxide (O2(-)) catalyzed BA photo modification and apoptosis in HaCaT keratinocytes under sunlight exposure. O2(-) generation was confirmed by quenching through superoxide dismutase (SOD). BA induced photocytotoxicity were investigated through MTT and NRU assay. We proposed DNA insults such as single and double strand breakage and CPDs formation which results in cell cycle arrest and apoptosis by photosensitized BA. BA induced apoptosis was caspase dependent and occurred through a mitochondrial pathway. Reduction of mitochondrial membrane potential, translocation of Bax to mitochondria and cytochrome c release favors involvement of mitochondria in BA phototoxicity. AO/EB double staining and TEM analysis also support apoptotic cell death. We propose a p21 regulated apoptosis via expression of Bax, and cleaved PARP under sunlight exposure. Thus, we conclude that it is imperative to avoid solar radiation during peak hr (between 11A.M. and 3P.M.) when the amount of solar radiation is high, in the light of DNA damage which may lead to mutation or skin cancer through photosensitized BA under sunlight exposure. Concomitantly, investigation is urgently required for the photosafety of BA photoproducts reaching in the environment through photomodification.
authors.affiliation: Photobiology Division, CSIR - Indian Institute of Toxicology Research, India; College of Pharmacy, Faculty of Pharmaceutical Sciences, Pt. B.D.S University of Health Sciences, Rohtak, Haryana, India.
authors.forename: Syed Faiz
authors.initials: SF
authors.lastname: Mujtaba
authors.affiliation: Photobiology Division, CSIR - Indian Institute of Toxicology Research, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Dwivedi
authors.affiliation: Photobiology Division, CSIR - Indian Institute of Toxicology Research, India; College of Pharmacy, Faculty of Pharmaceutical Sciences, Pt. B.D.S University of Health Sciences, Rohtak, Haryana, India.
authors.forename: Neera
authors.initials: N
authors.lastname: Yadav
authors.affiliation: Analytical Chemistry, CSIR - Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Ratnasekhar
authors.initials: R
authors.lastname: Ch
authors.affiliation: Photobiology Division, CSIR - Indian Institute of Toxicology Research, India.
authors.forename: Hari Narayan
authors.initials: HN
authors.lastname: Kushwaha
authors.affiliation: Analytical Chemistry, CSIR - Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Mohana K R
authors.initials: MK
authors.lastname: Mudiam
authors.affiliation: College of Pharmacy, Faculty of Pharmaceutical Sciences, Pt. B.D.S University of Health Sciences, Rohtak, Haryana, India.
authors.forename: Gajendra
authors.initials: G
authors.lastname: Singh
authors.affiliation: Photobiology Division, CSIR - Indian Institute of Toxicology Research, India. Electronic address: ratanray.2011@rediffmail.com.
authors.forename: Ratan S
authors.initials: RS
authors.lastname: Ray
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D001551:Benz(a)Anthracenes / Q000032:analysis / Q000737:chemistry / Q000633:toxicity*; D002384:Catalysis; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects* / Q000528:radiation effects; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008027:Light; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000737:chemistry* / Q000378:metabolism; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D001551:Benz(a)Anthracenes; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051028:bcl-2-Associated X Protein; D013481:Superoxides; C030935:benz(a)anthracene; D011065:Poly(ADP-ribose) Polymerases