Arranz Nuria, Haza Ana I, García Almudena, Möller Lennart, Rafter Joseph, Morales Paloma
Departamento de Nutrición, Bromatología y Tecnología de los Alimentos, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain.
J Appl Toxicol. 2006 Nov-Dec;26(6):493-9. doi: 10.1002/jat.1168.
The aim of this study was to investigate the protective effect of isothiocyanates towards N-nitrosamine-induced DNA damage in the single-cell gel electrophoresis (SCGE)/HepG2 assay. None of the isothiocyanates (ITCs) concentrations tested in the presence or absence of formamidopyrimidine-DNA glycosylase (Fpg), caused DNA damage per se. Combined treatments of HepG2 cells with phenethyl isothiocyanate (PEITC), allyl isothiocyanate (AITC) or indol-3-carbinol (I3C) and N-nitrosopyrrolidine (NPYR) or N-nitrosodimethylamine (NDMA) reduced the genotoxic effects of the N-nitrosamines in a dose-dependent manner. The protective effect of the three ITCs tested was higher towards NPYR-induced oxidative DNA damage than against NDMA. The greatest protective effect towards NPYR-induced oxidative DNA damage was shown by I3C (1 microm, 79%) and by PEITC (1 microm, 67%) and I3C (1 microm, 61%) towards NDMA (in the presence of Fpg enzyme). However, in the absence of Fpg enzyme, AITC (1 microm, 72%) exerted the most drastic reduction towards NPYR-induced oxidative DNA damage, and PEITC (1 microm, 55%) towards NDMA. The results indicate that ITCs protect human-derived cells against the DNA damaging effect of NPYR and NDMA, two carcinogenic compounds which occur in the environment.
本研究旨在通过单细胞凝胶电泳（SCGE）/HepG2试验，研究异硫氰酸盐对N-亚硝胺诱导的DNA损伤的保护作用。无论是否存在甲酰胺嘧啶-DNA糖基化酶（Fpg），所测试的异硫氰酸盐（ITCs）浓度本身均未引起DNA损伤。用苯乙基异硫氰酸盐（PEITC）、烯丙基异硫氰酸盐（AITC）或吲哚-3-甲醇（I3C）与N-亚硝基吡咯烷（NPYR）或N-亚硝基二甲胺（NDMA）联合处理HepG2细胞，可剂量依赖性地降低N-亚硝胺的遗传毒性作用。所测试的三种ITCs对NPYR诱导的氧化性DNA损伤的保护作用高于对NDMA的保护作用。I3C（1微摩尔，79%）对NPYR诱导的氧化性DNA损伤显示出最大的保护作用，而PEITC（1微摩尔，67%）和I3C（1微摩尔，61%）对NDMA（在Fpg酶存在下）显示出最大的保护作用。然而，在不存在Fpg酶的情况下，AITC（1微摩尔，72%）对NPYR诱导的氧化性DNA损伤的降低作用最为显著，而PEITC（1微摩尔，55%）对NDMA诱导的氧化性DNA损伤的降低作用最为显著。结果表明，ITCs可保护人源细胞免受环境中存在的两种致癌化合物NPYR和NDMA的DNA损伤作用。
