Effects of arsenic and UVB on normal human cultured keratinocytes: Impact on apoptosis and implication on photocarcinogenesis
Effects of arsenic and UVB on normal human cultured keratinocytes: Impact on apoptosis and implication on photocarcinogenesis
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DOI：
10.1021/tx049834b
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发表时间：
2005-02-01
影响因子：
4.1
通讯作者：
Chen, GS
中科院分区：
文献类型：
--
作者：
Chen, PH;Lan, CCE;Chen, GS
无机砷是一种环境毒素和人类致癌物。砷作为一种协同诱变剂，可增强紫外线照射小鼠皮肤的致癌作用。细胞凋亡是一种受良好调控的细胞死亡过程，对细胞发育和组织稳态至关重要。细胞凋亡的失调会导致各种病理状态，如癌症。本研究的目的是探讨砷和UVB的相互作用对体外培养的人角质形成细胞的凋亡作用。培养的角质形成细胞用亚砷酸钠（1 μ M）和/或UVB 50 nJ/cm（2）照射以不同的组合处理，包括单独砷（As组）、单独UVB（UVB组）、砷后UVB（As/UVB组）和UVB后As（UVB/As组）处理。我们的研究结果表明，低浓度的亚砷酸钠并没有诱导角质形成细胞凋亡。TUNEL法显示UVB组caspase-8、caspase-9和caspase-3活性明显升高，并诱导细胞凋亡。在UVB/As组中观察到类似的促凋亡作用。与此相反，在As/UVB组中，仅注意到细胞形态和存活率的细微变化。Western blot和caspase-8、-9、-3活性检测结果显示，As/UVB组细胞凋亡信号通路和凋亡受体均未激活。因此，我们得出结论，预处理的角质形成细胞与亚砷酸钠减少了由UVB诱导的促凋亡作用。这一发现与研究砷和UVB致癌作用的动物模型相吻合。砷降低UVB诱导的细胞凋亡的分子机制仍有待阐明。
Inorganic arsenic is an environmental toxin and a human carcinogen. Being a co-mutagen, arsenic enhances carcinogenesis of ultraviolet irradiation on the mouse skin. Apoptosis, a well-regulated cell death process, is essential for cell development and tissue homeostasis. Dysregulation of apoptosis will lead to various kinds of pathological conditions, such as cancers. The purpose of this study is to investigate the apoptotic effect induced by the interactions of arsenic and UVB on cultured human keratinocytes. Cultured keratinocytes were treated with sodium arsenite (1 muM) and/or UVB 50 nJ/cm(2) irradiation in different combinations, including arsenic alone (As group), UVB alone (UVB group), arsenic followed by UVB (As/UVB group), and UVB followed by As (UVB/As group) treatments. Our results revealed that a low concentration of sodium arsenite did not induce keratinocytes apoptosis. The UVB group showed obvious elevation of caspase-8, -9, and -3 activities in addition to strong induction of apoptosis as determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine nick-end labeling (TUNEL) assay. Similar pro-apoptotic effects were observed in the UVB/As group. In contrast, only subtle changes of cell morphology and survival rate were noticed in the As/UVB group. In addition, the results of Western blot and activity assay of caspase-8, -9, and -3 revealed that neither the receptor nor the mitochondrial apoptotic signaling pathway was activated in the As/UVB group. Therefore, we conclude that the pretreatment of keratinocytes with sodium arsenite decreased the pro-apoptotic effects induced by UVB. This finding corroborated with the animal model studying the effects of arsenic and UVB on carcinogenesis. The molecular mechanisms by which arsenic decreased UVB-induced apoptosis remain to be elucidated.