1. 1-Methoxy-3-indolylmethyl glucosinolate; a potent genotoxicant in bacterial and mammalian cells: Mechanisms of bioactivation
- Author
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Chimgee Baasanjav-Gerber, Fabian Schumacher, Albrecht Seidel, Monika Schreiner, Hansruedi Glatt, Wolfram Engst, Bernhard H. Monien, and Heinz Frank
- Subjects
Salmonella typhimurium ,congenital, hereditary, and neonatal diseases and abnormalities ,Indoles ,Magnetic Resonance Spectroscopy ,Glucosinolates ,Sister chromatid exchange ,Gene mutation ,Biology ,Toxicology ,medicine.disease_cause ,Chinese hamster ,Cell Line ,chemistry.chemical_compound ,Cricetulus ,Cricetinae ,otorhinolaryngologic diseases ,medicine ,Animals ,Humans ,Biotransformation ,Mutation ,Myrosinase ,food and beverages ,General Medicine ,biology.organism_classification ,chemistry ,Biochemistry ,Cell culture ,Hypoxanthine-guanine phosphoribosyltransferase ,Glucosinolate ,Mutagens - Abstract
1-Methoxy-3-indolylmethyl (1-MIM) glucosinolate, contained in many Brassica vegetables, is strongly mutagenic in Salmonella typhimurium TA100 when activated by myrosinase. Here, we describe the synthesis and evaluation of two breakdown products, 1-MIM nitrile and 1-MIM alcohol. 1-MIM nitrile was not mutagenic and 1-MIM alcohol showed low direct mutagenicity in TA100, indicating that other breakdown products mediated the mutagenicity of 1-MIM glucosinoate/myrosinase in this strain. However, 1-MIM alcohol was strongly mutagenic to a TA100-derived strain expressing human sulphotransferase SULT1A1. Likewise, 1-MIM glucosinolate (with myrosinase) showed 10 times higher mutagenic activity in TA100-SULT1A1 than in strain TA100. Identical adducts, N2-(1-MIM)-dG and N6-(1-MIM)-dA, were detected in both strains, but the levels were higher in TA100-hSULT1A1. A similar influence of SULT1A1 was observed in recombinant V79-hSULT1A1 cells compared to parental SULT-deficient Chinese hamster V79 cells. 1-MIM glucosinolate (with myrosinase) as well as 1-MIM alcohol induced sister chromatid exchange in both cell lines, but with clearly higher efficiency in V79-hSULT1A1 cells. Gene mutation assays were conducted at the HPRT locus with 1-MIM alcohol in V79-hSULT1A1 cells, and with 1-MIM glucosinolate/myrosinase in V79 parental cells. In both cases, the result was clearly positive. Thus, 1-MIM glucosinolate is mutagenic in bacterial and mammalian cells via at least two different metabolites.
- Published
- 2011