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.