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Induction of keratinocyte apoptosis by photosensitizing chemicals plus UVA.

Abstract：

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.

journal_name

J Dermatol Sci

journal_title

Journal of dermatological science

authors

Kurita M,Shimauchi T,Kobayashi M,Atarashi K,Mori K,Tokura Y

doi

10.1016/j.jdermsci.2006.10.010

subject

Has Abstract

pub_date

2007-02-01 00:00:00

pages

105-12

issue

2

eissn

0923-1811

issn

1873-569X

pii

S0923-1811(06)00316-1

journal_volume

45

pub_type

杂志文章

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