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

Abstract

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.