Protective effects of organosulfur compounds 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 organosulfur compounds towards N-nitrosamine-induced DNA damage in the single-cell gel electrophoresis (SCGE)/HepG2 assay. N-Nitrosopyrrolidine (NPYR) and N-nitrosodimethylamine (NDMA) incubated with formamidopyrimidine-DNA glycosylase (Fpg), caused a significant increase in oxidative DNA damage in comparison to the solvent control, the lowest effective concentrations, being 5 and 27 mM, respectively. NPYR exerted greater genotoxic effects than NDMA. None of the organosulfur compounds (OSCs) concentrations tested in presence or absence of Fpg enzyme, caused DNA damage per se. OSCs (diallyl sulfide, DAS and dipropyl sulfide, DPS, 1-50 microM; diallyl disulfide, DADS and dipropyl disulfide, DPDS, 1-5 microM) reduced the genotoxic effects of the N-nitrosamines in a dose-dependent manner when HepG2 cells were simultaneously treated with OSCs and N-nitrosamines. The effect of NPYR was attenuated by about 61-67%, respectively, with the highest concentration of DAS (50 microM) and DADS (5 microM). The protective effect of DADS (5 microM, 66%) was higher than DAS (50 microM, 53%) towards NDMA-induced oxidative DNA damage. A concentration of 50 microM DPS and 5 microM DPDS led to a 65-63% and 59-65% reduction in NPYR/NDMA-induced oxidative DNA damage, respectively. Our results indicate that OSCs protect human-derived cells against the oxidative DNA damaging effect of NPYR and NDMA, two carcinogenic compounds which occur in the environment.