title: Induction of oxidative cell damage by photo-treatment with zinc meta N-methylpyridylporphyrin.
abstract: We have previously reported that isomeric Zn(II) N-methylpyridylporphyrins (ZnTM-2(3,4)-PyP4 + ) can act as photosensitizers with efficacy comparable to that of hematoporphyrin derivative (HpD) in preventing cell proliferation and causing cell death in vitro. To better understand the biochemical basis of this activity, the effects of photo-activated ZnTM-3-PyP4 + on GSH/GSSG ratio, lipid peroxidation, membrane permeability, oxidative DNA damage, and the activities of SOD, catalase, glutathione reductase, and glutathione peroxidase were evaluated. Light exposure of ZnTM-3-PyP4 + -treated colon adenocarcinoma cells caused a wide spectrum of oxidative damage including depletion of GSH, inactivation of glutathione reductase and glutathione peroxidase, oxidative DNA damage and peroxidation of membrane lipids. Cell staining with Hoechst-33342 showed morphological changes consistent with both necrotic and apoptotic death sequences, depending upon the presence of oxygen.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Kuwait University, Safat, Kuwait.
authors.forename: Dalal A
authors.initials: DA
authors.lastname: Al-Mutairi
authors.forename: James D
authors.initials: JD
authors.lastname: Craik
authors.forename: Ines
authors.initials: I
authors.lastname: Batinic-Haberle
authors.forename: Ludmil T
authors.initials: LT
authors.lastname: Benov
mesh_terms: D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D019803:Glutathione Disulfide / Q000187:drug effects / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008665:Metalloporphyrins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010787:Photosensitivity Disorders; D017319:Photosensitizing Agents / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism
chemical_list: D008665:Metalloporphyrins; D017319:Photosensitizing Agents; C017802:zinc hematoporphyrin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione; D019803:Glutathione Disulfide