Three structurally homologous isothiocyanates exert "Janus" characteristics in human HepG2 cells.
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 > or =10 microM MTPITC, > or =3 microM MTBITC, and > or =0.1 microM MTPeITC, respectively. In antigenotoxicity studies, the most effective concentration of MTPITC and MTPeITC toward B(a)P-induced DNA damage was 0.1 muM in both test systems. MTBITC suppressed MN formation in B(a)P-treated cells to the background level at a concentration of 1 muM. The ambivalent character of the ITCs under studymust be further clarified, especially in the possiblecontext of high dose therapeutic applications.
Lamy
Evelyn
E
Department of Environmental Health Sciences, University Medical Center Freiburg, Breisacher Strasse 115b, Freiburg 79106, Germany. evelyn.lamy@uniklinik-freiburg.de
Crössmann
Catharina
C
Saeed
Adal
A
Schreiner
Peter R
PR
Kotke
Mike
M
Mersch-Sundermann
Volker
V
D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D015394:Molecular Structure; D009153:Mutagens / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010945:Plants, Edible / Q000737:chemistry; D012044:Regression Analysis; D013329:Structure-Activity Relationship
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D009153:Mutagens