1-Methoxy-3-indolylmethyl glucosinolate; a potent genotoxicant in bacterial and mammalian cells: Mechanisms of bioactivation.
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, N(2)-(1-MIM)-dG and N(6)-(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.
Glatt
Hansruedi
H
German Institute of Human Nutrition, Potsdam-Rehbrücke, 14558 Nuthetal, Germany. glatt@dife.de
Baasanjav-Gerber
Chimgee
C
Schumacher
Fabian
F
Monien
Bernhard H
BH
Schreiner
Monika
M
Frank
Heinz
H
Seidel
Albrecht
A
Engst
Wolfram
W
D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005961:Glucosinolates / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D007211:Indoles / Q000493:pharmacokinetics / Q000633:toxicity*; D009682:Magnetic Resonance Spectroscopy; D009153:Mutagens / Q000493:pharmacokinetics / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism*
D005961:Glucosinolates; D007211:Indoles; D009153:Mutagens; C064701:1-methoxy-3-indolylmethylglucosinolate