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

J Appl Toxicol. 2006 Sep-Oct;26(5):466-73. doi: 10.1002/jat.1163.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / pharmacology*
  • Cell Line, Tumor
  • Comet Assay*
  • DNA / drug effects*
  • DNA Damage*
  • DNA-Formamidopyrimidine Glycosylase
  • Dimethylnitrosamine
  • Dose-Response Relationship, Drug
  • Humans
  • Indoles / pharmacology
  • Isothiocyanates / pharmacology*
  • Mutagens*
  • N-Nitrosopyrrolidine*
  • Nitrosamines*

Substances

  • Anticarcinogenic Agents
  • Indoles
  • Isothiocyanates
  • Mutagens
  • Nitrosamines
  • phenethyl isothiocyanate
  • DNA
  • allyl isothiocyanate
  • indole-3-carbinol
  • DNA-Formamidopyrimidine Glycosylase
  • Dimethylnitrosamine
  • N-Nitrosopyrrolidine