| Induction of keratinocyte apoptosis by photosensitizing chemicals plus UVA. | |
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MedLine Citation:
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PMID: 17141480 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The capacity of photosensitizing chemicals with ultraviolet A light (UVA) to induce apoptosis is one of the methods to assess their phototoxic and potentially photoallergic properties, since apoptotic cells may be easily presented by antigen-presenting cells. OBJECTIVES: We examined the photoaggravated ability to induce keratinocyte apoptosis of various chemicals that are known as causative agents of photocontact dermatitis and drug photosensitivity involving photoallergic and/or phototoxic mechanisms. METHODS: HaCaT keratinocytes were incubated with 3,3',4',5-tetrachlorosalicylanilide (TCSA), bithionol, diphenylhydramine, chlorpromazine, 6-methylcoumarin, sparfloxacin, and enoxacin at 10(-7) to 10(-4)M and irradiated with UVA at 4J/cm(2). As positive control, 8-methoxypsoralen (8-MOP) was also tested. Apoptosis and necrosis were evaluated by flow cytometric enumeration of annexin V(+) 7-AAD(-) and annexin V(+) 7-AAD(+) cells, respectively. The expression of apoptosis-related molecules, caspase-3 and poly (ADP-ribose) polymerase (PARP), was tested by flow cytometric and Western blotting analyses. RESULTS: In a comparison with non-irradiated cells, significant apoptosis was found in TCSA, bithionol, chlorpromazine, sparfloxacin and enoxacin at 10(-4) or 10(-5)M as well as 8-MOP as assessed by both annexin V and active caspase-3 stainings, while necrosis occurred in most of these chemicals at 10(-4)M. Neither apoptosis nor necrosis was seen in diphenylhydramine or 6-methylcoumarin. PARP were activated in HaCaT cells phototreated with TCSA, bithionol and chlorpromazine. CONCLUSIONS: We suggest that our method is useful for in vitro assessment of phototoxicity and potential photoallergenicity of chemicals. |
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Authors:
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Masako Kurita; Takatoshi Shimauchi; Miwa Kobayashi; Kenji Atarashi; Koji Mori; Yoshiki Tokura |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-12-01 |
Journal Detail:
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Title: Journal of dermatological science Volume: 45 ISSN: 0923-1811 ISO Abbreviation: J. Dermatol. Sci. Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2007-01-22 Completed Date: 2007-03-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9011485 Medline TA: J Dermatol Sci Country: Netherlands |
Other Details:
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Languages: eng Pagination: 105-12 Citation Subset: IM |
Affiliation:
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Department of Dermatology, University of Occupational and Environmental Health, Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anesthetics, Local
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pharmacology Anti-Infective Agents, Local / pharmacology Antipsychotic Agents / pharmacology Antitubercular Agents / pharmacology Apoptosis / drug effects*, radiation effects* Bithionol / pharmacology Cell Line, Transformed Chlorpromazine / pharmacology Coumarins / pharmacology Diphenhydramine / pharmacology Enoxacin / pharmacology Enzyme Inhibitors / pharmacology Fluoroquinolones / pharmacology Humans Keratinocytes / cytology, drug effects*, radiation effects* Necrosis Photosensitizing Agents / pharmacology* Salicylanilides / pharmacology Ultraviolet Rays* |
| Chemical | |
Reg. No./Substance:
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0/Anesthetics, Local; 0/Anti-Infective Agents, Local; 0/Antipsychotic Agents; 0/Antitubercular Agents; 0/Coumarins; 0/Enzyme Inhibitors; 0/Fluoroquinolones; 0/Photosensitizing Agents; 0/Salicylanilides; 111542-93-9/sparfloxacin; 1154-59-2/3,3',4',5-tetrachlorosalicylanilide; 50-53-3/Chlorpromazine; 58-73-1/Diphenhydramine; 74011-58-8/Enoxacin; 92-48-8/6-methylcoumarin; 97-18-7/Bithionol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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