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Three structurally homologous isothiocyanates exert “Janus” characteristics in human HepG2 cells
Author(s) -
Lamy Evelyn,
Crößmann Catharina,
Saeed Adal,
Schreiner Peter R.,
Kotke Mike,
MerschSundermann Volker
Publication year - 2009
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20470
Subject(s) - genotoxicity , dna damage , mutagen , micronucleus test , micronucleus , chemistry , potency , gel electrophoresis , microbiology and biotechnology , dna , in vitro , biochemistry , toxicity , biology , organic chemistry
In this study, we used the single cell gel electrophoresis (SCGE) assay and the micronucleus (MN) test to investigate the DNA damaging effects and the antigenotoxic potencies of three structurally related ITCs in human HepG2 cells. The results show that all three ITCs possess the characteristic of a “Janus” compound, i.e., they exert both significant genotoxicity and antigenotoxicity, depending on the concentrations used in the test systems applied. Regression line analysis of the results derived by SCGE analysis showed genotoxic potency of the ITCs in the following order: 3‐methylthiopropyl ITC (MTPITC) > 4‐methylthiobutyl ITC (MTBITC) > 5‐methylthiopentyl ITC (MTPeITC); however, this order in genotoxic potency was not confirmed by MN analysis. Additionally, the MN test showed significant mutagenicity of the test substances at higher concentrations when compared with the SCGE assay. Twenty‐four hour‐treatment of the cells with the ITCs, followed by a 1‐hr recovery period, showed significant DNA repair in the SCGE assay at a concentration ≥10 μM MTPITC, ≥3 μM MTBITC, and ≥0.1 μM MTPeITC, respectively. In antigenotoxicity studies, the most effective concentration of MTPITC and MTPeITC toward B(a)P‐induced DNA damage was 0.1 μM in both test systems. MTBITC suppressed MN formation in B(a)P‐treated cells to the background level at a concentration of 1 μM. The ambivalent character of the ITCs under studymust be further clarified, especially in the possiblecontext of high dose therapeutic applications. Environ. Mol. Mutagen. 2009. © 2009 Wiley‐Liss, Inc.