Formation of hepatic DNA adducts by methyleugenol in mouse models: drastic decrease by Sult1a1 knockout and strong increase by transgenic human SULT1A1/2.

@article{Herrmann2014FormationOH,
  title={Formation of hepatic DNA adducts by methyleugenol in mouse models: drastic decrease by Sult1a1 knockout and strong increase by transgenic human SULT1A1/2.},
  author={Kristin Herrmann and Wolfram Engst and Walter Meinl and Simone Florian and Alexander T. Cartus and Dieter Schrenk and Klaus Erich Appel and Tobias Nolden and Heinz Himmelbauer and Hansruedi Glatt},
  journal={Carcinogenesis},
  year={2014},
  volume={35 4},
  pages={
          935-41
        }
}
Methyleugenol--a natural constituent of herbs and spices--is hepatocarcinogenic in rodent models. It can form DNA adducts after side-chain hydroxylation and sulfation. We previously demonstrated that human sulfotransferases (SULTs) 1A1 and 1A2 as well as mouse Sult1a1, expressed in Salmonella target strains, are able to activate 1'-hydroxymethyleugenol (1'-OH-ME) and 3'-hydroxymethylisoeugenol (3'-OH-MIE) to mutagens. Now we investigated the role of these enzymes in the formation of hepatic DNA… 

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References

SHOWING 1-10 OF 52 REFERENCES

Identification of human and murine sulfotransferases able to activate hydroxylated metabolites of methyleugenol to mutagens in Salmonella typhimurium and detection of associated DNA adducts using UPLC-MS/MS methods.

Several methyleugenol metabolites are activated to DNA-reactive mutagens in S. typhimurium upon incorporation of appropriate sulfation capacity and methods were developed that may be utilised to analyse DNA samples from human tissues specifically for the possible presence of methyle Eugenol adducts.

Altered tissue distribution of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-DNA adducts in mice transgenic for human sulfotransferases 1A1 and 1A2.

Soluble sulfotransferases (SULTs) generate electrophilically reactive metabolites from numerous food-borne compounds, environmental contaminants and drugs, often resulting in mutagenicity and

Inhibition of sulfotransferase affecting in vivo genotoxicity and DNA adducts induced by safrole in rat liver.

It is suggested that safrole is capable of inducing SCEs, chromosomal aberrations, and RDS in the rat liver in vivo and that these effects may be induced by the sulfuric acid ester metabolite that can bind DNA.

32P-post-labelling analysis of DNA adducts formed in the livers of animals treated with safrole, estragole and other naturally-occurring alkenylbenzenes. II. Newborn male B6C3F1 mice.

All but one of the alkenylbenzenes studied became bound to newborn mouse-liver DNA, but the levels and the persistence of adducts formed by the carcinogenic compounds were greater.

Structure-activity studies of the carcinogenicities in the mouse and rat of some naturally occurring and synthetic alkenylbenzene derivatives related to safrole and estragole.

Twenty-three naturally occurring and synthetic alkenylbenzene derivatives structurally related to the hepatocarcinogen safrole were assayed for their hepatocARCinogenicity in mice to identify benign skin tumors that could be promoted with croton oil.

Strong evidence from studies with brachymorphic mice and pentachlorophenol that 1'-sulfoöxysafrole is the major ultimate electrophilic and carcinogenic metabolite of 1'-hydroxysafrole in mouse liver.

Data strongly support the conclusion that 1'-sulfoöxysafrole is the major ultimate electrophilic and tumor-initiating metabolite of 1'-hydroxysaf role.

Metabolism of methyleugenol in liver microsomes and primary hepatocytes: pattern of metabolites, cytotoxicity, and DNA-adduct formation.

A virtually complete pattern of microsomal (rat, bovine, and human) and hepatocellular (rat) metabolites of 1 are presented suggesting the formation of several reactive metabolites possibly involved in carcinogenicity, organ toxicity, and immune reactions.

Inhibition of methyleugenol bioactivation by the herb-based constituent nevadensin and prediction of possible in vivo consequences using physiologically based kinetic modeling.

  • A. Al-SubeihiW. Alhusainy I. Rietjens
  • Biology
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 2013

Genotoxic potential of methyleugenol and selected methyleugenol metabolites in cultured Chinese hamster V79 cells.

Methyleugenol is a substituted alkenylbenzene classified by the European Union's Scientific Committee on Food as a genotoxic carcinogen. We addressed cytotoxicity, genotoxicity and mutagenicity

Comparative induction of unscheduled DNA synthesis in cultured rat hepatocytes by allylbenzenes and their 1'-hydroxy metabolites.

  • V. S. ChanJ. Caldwell
  • Chemistry, Biology
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 1992
...