Genotoxic effects of methyl isothiocyanate.
Aim of the study was to investigate the genotoxic effects of methyl isothiocyanate (MITC), a compound widely distributed in the environment as a constituent of certain vegetables, a soil fumigant and breakdown product of carbamate pesticides. MITC caused only marginal mutation induction in reversion assays with Salmonella strains TA100 and TA98 and, the maximum effect (<2-fold increase over the background rate) was seen at 100microg/ml. In differential DNA-repair assays with E. coli (strains 343/763 uvrB/recA and 343/765 uvr(+)/rec(+)), a pronounced dose-response effect (induction of repairable DNA-damage) was seen at low concentrations (>/=4microg/ml). In both bacterial assays, addition of activation mix (rat liver S-9) led to a reduction of the genotoxic effects. In micronucleus assay and in single cell gel electrophoresis assay with human hepatoma cells (HepG2), clear cut positive results were obtained at exposure concentrations of <5microg/ml. On the contrary, only marginal effects were seen in differential DNA-repair host-mediated assays where E. coli indicator cells were recovered from different inner organs of mice that had been treated orally with a high dose (90mg/kg bw) of the test compound. Further in vitro experiments showed that MITC is inactivated by body fluids (saliva, gastric juice) and that its DNA-damaging properties are attenuated by non-enzymatic protein binding. Since exposure of HepG2 cells to MITC led to formation of thiobarbituric acid reactive substances, it is likely that its DNA-damaging effects involve lipid peroxidation processes. Overall, our findings show that MITC induces only marginal effects at extremely high (almost lethal) doses in inner organs in vivo, but it causes DNA-damage at low concentrations in vitro.
Kassie
F
F
Institute for Tumor Biology and Cancer Research, University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria.
Laky
B
B
Nobis
E
E
Kundi
M
M
Knasmüller
S
S
D000328:Adult; D000818:Animals; D006528:Carcinoma, Hepatocellular; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D005750:Gastric Juice / Q000187:drug effects / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D006639:Histidine / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic; D017879:Isothiocyanates / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D012463:Saliva / Q000187:drug effects / Q000378:metabolism; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D018675:Toxicity Tests / Q000379:methods*; D014407:Tumor Cells, Cultured
D006540:Herbicides; D017879:Isothiocyanates; D017392:Thiobarbituric Acid Reactive Substances; D006639:Histidine; C005227:methyl isothiocyanate