Abstracts Biological Sciences

Methyleugenol: Studies in metabolism and effects on hepatic DNA

by Jennifer Lewis Burkey

Methyleugenol is a component of essential oils and is found in many foods and consumer products. Structurally similar to safrole, a known rodent carcinogen, methyleugenol has been shown to be a potent rodent hepatocarcinogen in a National Toxicology Program two-year bioassay. The mechanism by which methyleugenol causes tumors is suspected to mimic that of safrole. However, it is unknown if methyleugenol produces metabolites analogous to the proximate carcinogens of safrole. The hypothesis of this study is that methyleugenol is a genotoxicant after metabolic activation. The data presented show that methyleugenol is rapidly excreted from the body of rodents after oral and IV dose, primarily in the urine. Metabolites found in the urine include hydroxylated derivatives that are subsequently conjugated. The same basic pattern of metabolites is produced in isolated hepatocytes and microsomes from both rodents and humans. Mice produce more of these metabolites and at a faster rate than do rat or human derived systems. Among the metabolites identified in microsomes is 1 '-hydroxymethyleugenol, the analogous metabolite to the proximate carcinogen of safrole. Results of the Unscheduled DNA synthesis assay in hepatocytes show that methyleugenol is positive (genotoxic) in both rats and mice but possibly much less so in human derived hepatocytes, and that genotoxicity can be blocked by preventing sulfation in rodent hepatoctyes. Thus methyleugenol is capable of forming the proximate carcinogenic molecule (1' - hydroxymethyleugenol) and the subsequent sulfation of that molecule may lead to the moiety responsible for DNA damage and potentially eventual tumorigenesis.