Protective effects of isothiocyanates towards N-nitrosamine-induced DNA damage in the single-cell gel electrophoresis (SCGE)/HepG2 assay.
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 presence of Fpg enzyme). However, in 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. 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.
Arranz
Nuria
N
Departamento de Nutrición, Bromatología y Tecnología de los Alimentos, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Haza
Ana I
AI
García
Almudena
A
Möller
Lennart
L
Rafter
Joseph
J
Morales
Paloma
P
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D020552:Comet Assay; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D043382:DNA-Formamidopyrimidine Glycosylase; D004128:Dimethylnitrosamine; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D017879:Isothiocyanates / Q000494:pharmacology*; D009153:Mutagens; D009242:N-Nitrosopyrrolidine; D009602:Nitrosamines
D016588:Anticarcinogenic Agents; D007211:Indoles; D017879:Isothiocyanates; D009153:Mutagens; D009602:Nitrosamines; C058305:phenethyl isothiocyanate; D004247:DNA; C004471:allyl isothiocyanate; C016517:indole-3-carbinol; D043382:DNA-Formamidopyrimidine Glycosylase; D004128:Dimethylnitrosamine; D009242:N-Nitrosopyrrolidine