title: Role of type I & type II reactions in DNA damage and activation of caspase 3 via mitochondrial pathway induced by photosensitized benzophenone.
abstract: Sunscreen users have been increased, since excessive sun exposure increased the risk of skin diseases. Benzophenone (BP) and its derivatives are commonly used in sunscreens as UV blocker. Its photosafety is concern for human health. Our study showed the role of type-I and type-II radicals in activation of caspase 3 and phototoxicity of BP under sunlight/UV radiation. BP photodegraded and formed two photoproducts. BP generates reactive oxygen species (ROS) singlet oxygen ((1)O2), superoxide anion (O2˙(-)) and hydroxyl radical (˙OH) through type-I and type-II photodynamic mechanisms. Photocytotoxicity significantly reduced cell viability under sunlight, UVB and UVA. DCF fluorescence confirmed intracellular ROS generation. BP showed single strand DNA breakage, further proved by cyclobutane pyrimidine dimmers (CPDs) formation. Lipid peroxidation and LDH leakage were enhanced by BP. P21 dependent cell cycle study showed sub G1 population which advocates apoptotic cell death, confirmed through AO/EB and annexin V/PI staining. BP decreased mitochondrial membrane potential, death protein released and activated caspase. We proposed cytochrome c regulated caspase 3 dependent apoptosis in HaCaT cell line through down regulation of Bcl2/Bax ratio. Phototoxicity potential of its photoproducts is essential to understand its total environmental fate. Hence, we conclude that BP may replace from cosmetics preparation of topical application.
authors: Photobiology Division, CSIR - Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226001, India; Academy of Scientific and Innovative Research, CSIR-IITR Campus, Lucknow, India.
authors: Saroj Kumar
authors: SK
authors: Amar
authors: Photobiology Division, CSIR - Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226001, India; Academy of Scientific and Innovative Research, CSIR-IITR Campus, Lucknow, India.
authors: Shruti
authors: S
authors: Goyal
authors: Photobiology Division, CSIR - Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226001, India.
authors: Syed Faiz
authors: SF
authors: Mujtaba
authors: Photobiology Division, CSIR - Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226001, India.
authors: Ashish
authors: A
authors: Dwivedi
authors: Photobiology Division, CSIR - Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226001, India.
authors: Hari Narayan
authors: HN
authors: Kushwaha
authors: Photobiology Division, CSIR - Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226001, India.
authors: Ankit
authors: A
authors: Verma
authors: Photobiology Division, CSIR - Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226001, India.
authors: Deepti
authors: D
authors: Chopra
authors: Developmental Toxicology, CSIR - Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226001, India.
authors: Rajnish K
authors: RK
authors: Chaturvedi
authors: Photobiology Division, CSIR - Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226001, India. Electronic address: ratanray.2011@rediffmail.com.
authors: Ratan Singh
authors: RS
authors: Ray
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D001577:Benzophenones / Q000528:radiation effects / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053904:DNA Breaks, Single-Stranded; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D010782:Photolysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018570:Risk Assessment; D015398:Signal Transduction; D013473:Sunscreening Agents / Q000528:radiation effects / Q000633:toxicity*; D013481:Superoxides / Q000378:metabolism; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C000595707:BCL2 protein, human; D001577:Benzophenones; D019253:Proto-Oncogene Proteins c-bcl-2; D013473:Sunscreening Agents; D051028:bcl-2-Associated X Protein; D013481:Superoxides; D017665:Hydroxyl Radical; C047723:benzophenone; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Apoptosis; Benzophenone; DNA damage; Phototoxicity; Sunscreens; UV-radiation