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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
Author(s) -
García Almudena,
Haza Ana I.,
Arranz Nuria,
Rafter Joseph,
Morales Paloma
Publication year - 2008
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1270
Subject(s) - phenethyl isothiocyanate , chemistry , dna damage , biochemistry , carcinogen , cyp2e1 , oxidative phosphorylation , apoptosis , pharmacology , microbiology and biotechnology , dna , cytochrome p450 , biology , enzyme
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 (I3C) alone showed a weak protective effect towards NDBA (0.1 µ m , 26–27%, respectively) or NPIP (1 µ 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, I3C and AITC in combination with vitamin C showed a stronger inhibition of oxidative DNA‐damage induced by NDBA (0.1 µ m , 67%, 42%, 32%, respectively) or NPIP (1 µ 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 I3C strongly inhibited the p ‐nitrophenol hydroxylation (CYP2E1) activity (0.1 µ m , 66–50%, respectively), while the coumarin hydroxylase (CYP2A6) activity was slightly reduced (0.1 µ m , 25–37%, respectively). However, the ethoxyresorufin O‐deethylation (CYP1A1) activity was only inhibited by PEITC (1 µ m , 55%). The results indicate that PEITC and I3C alone or PEITC, I3C 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 © 2007 John Wiley & Sons, Ltd.