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The glucosinolate metabolite 1‐methoxy‐3‐indolylmethyl alcohol induces a gene expression profile in mouse liver similar to the expression signature caused by known genotoxic hepatocarcinogens
Author(s) -
Ehlers Anke,
Florian Simone,
Schumacher Fabian,
Meinl Walter,
Lenze Dido,
Hummel Michael,
Heise Tanja,
Seidel Albrecht,
Glatt Hansruedi,
Lampen Alfonso
Publication year - 2015
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201400707
Subject(s) - gene expression , signature (topology) , biology , metabolite , microbiology and biotechnology , gene , glucosinolate , genetics , biochemistry , geometry , mathematics , agronomy , brassica
Scope Breakdown products of certain glucosinolates induce detoxifying enzymes and demonstrate preventive activities against chemically induced tumourigenesis in animal models. However, other breakdown products are genotoxic. 1‐Methoxy‐3‐indolylmethyl alcohol (1‐MIM‐OH) is mutagenic in bacterial and mammalian cells upon activation by sulphotransferases and forms DNA adducts in mouse tissues. This effect is enhanced in mice transgenic for human sulphotransferases 1A1/2 (FVB/N‐hSULT1A1/2). Therefore, we explored gene expression changes induced by 1‐MIM‐OH in mouse liver. Methods and results FVB/N‐hSULT1A1/2 mice were orally treated with 1‐MIM‐OH for 21 or 90 days, leading to high levels of hepatic 1‐MIM‐DNA adducts. Genome‐wide expression analyses demonstrated no influence on detoxifying enzymes, but up‐regulation of many mediators of the tumour suppressor p53 and down‐regulation of Fhit and other long genes. While this p53 response might indicate protection, it was unable to prevent the accumulation of DNA adducts. However, various epidemiological studies reported inverse associations between the intake of cruciferous vegetables and cancer. This association may be due to the presence of other glucosinolates with tumour‐preventing influences possibly outweighing adverse effects of some metabolites. Conclusion 1‐MIM‐OH is a genotoxic substance inducing a gene expression profile similar to the expression signature caused by known genotoxic hepatocarcinogens.