Protective effects of isothiocyanates alone or in combination with vitamin C towards N-nitrosodibutylamine or N-nitrosopiperidine-induced oxidative DNA damage in the single-cell gel electrophoresis (SCGE)/HepG2 assay
Protective effects of isothiocyanates alone or in combination with vitamin C towards N-nitrosodibutylamine or N-nitrosopiperidine-induced oxidative DNA damage in the single-cell gel electrophoresis (SCGE)/HepG2 assay
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DOI：
10.1002/jat.1270
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发表时间：
2008-03-01
影响因子：
3.3
通讯作者：
Morales, Paloma
中科院分区：
文献类型：
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作者：
Garcia, Almudena;Haza, Ana I.;Morales, Paloma
本研究的目的是在单细胞凝胶电泳法(SCGE/HepG2)中观察异硫氰酸酯单独或与维生素C合用对N-亚硝基二丁胺(NDBA)或N-亚硝基哌啶(NPIP)所致DNA氧化损伤的保护作用。单独使用异硫氰酸苯乙酯(PEITC)和吲哚-3-甲醇(13C)对NDBA(0.1微米，26-27%)或NPIP(1微米，26-28%)诱导的DNA氧化损伤的保护作用较弱。单用异硫氰酸烯丙酯(AITC)并不能减弱NDBA或NPIP引起的遗传毒性效应。相反，PEITC、13C和AITC联合维生素C对NDBA(0.1gm，67%，42%，32%)或NPIP(1微米，50%，73%，63%)诱导的DNA氧化损伤的抑制作用强于单独使用异硫氰酸酯(ITCs)。ITCs单独或与维生素C联用对N-亚硝胺诱导的DNA氧化损伤具有保护作用的一个可行机制可能是通过抑制其依赖的细胞色素P450的生物激活。PEITC和13C对对硝基苯酚羟化(CYP2E1)活性有较强的抑制作用(分别为0.1µm，66-50%)，而香豆素羟基酶(CYP2A6)活性略有降低(分别为0.1µm，25%-37%)。然而，乙氧基间苯二酚O-脱乙基酶(CYP1A1)活性仅被PEITC(1微米，55%)抑制。结果表明，单独使用PEITC和13C，或PEITC、13C和AITC与维生素C联合使用，可以保护人类来源的细胞免受两种食品致癌化合物NDBA和NPIP的DNA氧化损伤。版权所有(C)2007 John Wiley&Sons，Ltd.
The aim of this study was to investigate the protective effect of isothiocyanates alone or in combination with vitamin C towards N-nitrosodibutylamine (NDBA) or N-nitrosopiperidine (NPIP)-induced oxidative DNA damage in the single cell gel electrophoresis (SCGE)/HepG2 assay. Phenethyl isothiocyanate (PEITC) and indole-3-carbinol (13C) alone showed a weak protective effect towards NDBA (0.1 mu m, 26-27%, respectively) or NPIP (1 mu m, 26-28%, respectively)induced oxidative DNA damage. Allyl isothiocyanate (AITC) alone did not attenuate the genotoxic effect provoked by NDBA or NPIP. In contrast, HepG2 cells simultaneously treated with PEITC, 13C and AITC in combination with vitamin C showed a stronger inhibition of oxidative DNA-damage induced by NDBA (0.1 gm, 67%, 42%, 32%, respectively) or NPIP (1 mu m, 50%, 73%, 63%, respectively) than isothiocyanates (ITCs) alone. One feasible mechanism by which ITCs alone or in combination with vitamin C exert their protective effects towards N-nitrosamine-induced oxidative DNA damage could be by the inhibition of their cytochrome P450 dependent bioactivation. PEITC and 13C strongly inhibited the p-nitrophenol hydroxylation (CYP2E1) activity (0.1 mu m, 66-50%, respectively), while the coumarin hydroxylase (CYP2A6) activity was slightly reduced (0.1 mu m, 25-37%, respectively). However, the ethoxyresorufin O-deethylation (CYP1A1) activity was only inhibited by PEITC (1 mu m, 55%). The results indicate that PEITC and 13C alone or PEITC, 13C and AITC in combination with vitamin C protects human-derived cells against the oxidative DNA damaging effects of NDBA and NPIP, two food carcinogenic compounds. Copyright (C) 2007 John Wiley & Sons, Ltd.