4.5 Article

Protective effects of isothiocyanates towards N-nitrosamine-induced DNA damage in the single-cell gel electrophoresis (SCGE)/HepG2 assay

Journal

JOURNAL OF APPLIED TOXICOLOGY
Volume 26, Issue 5, Pages 466-473

Publisher

WILEY
DOI: 10.1002/jat.1163

Keywords

isothiocyanates compounds; N-nitrosamines; comet assay

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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 mu m, 79 %) and by PEITC (1 mu m, 67 %) and 13C (1 mu m, 61 %) towards NDMA (in presence of Fpg enzyme). However, in absence of Fpg enzyme, AITC (1 mu m, 72%) exerted the most drastic reduction towards NPYR-induced oxidative DNA damage, and PEITC (1 mu m, 55%) towards NDMA. Our results indicate that ITCs protect human-derived cells against the DNA damaging effect of NPYR and NDMA, two carcinogenic compounds that occur in the environment. Copyright (c) 2006 John Wiley & Sons, Ltd.

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