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@phdthesis{Ellis:2008,
author = {Ellis, JK},
title = {Studies on the Molecular Basis of Methyl Eugenol Carcinogenicity},
year = {2008}
}
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TY - THES
AB - Methyl eugenol (ME) is a naturally occurring chemical found in many fruits and spices and is used as a flavour and fragrance in the food and cosmetic industries. ME has been shown to be a genotoxic hepatocarcinogen and form DNA adducts at high doses in rodents. It is possible that a previous two year NTP study in the rat over estimated the potential risk of methyl eugenol by administering the test material via a gavage dose regimen and at relatively high doses, which resulted in extensive gastric and hepatic toxicity.A low dose twenty eight day feeding study with F344 rats was undertaken at ME doses of 1, 5, 50 and 50 (gavage) mg/kg bw/day. This was intended to investigate the potential toxicity of ME at doses more representative of human exposure and via a dietary dose regimen. Tissue samples were macroscopically examined for signs of increased incidences of lesions, particularly the stomach and liver. Tissue samples were also assessed for hepatic proliferating cell nuclear antigen (PCNA) levels using a 96 well plate ELISA technique, pre- and post-study plasma gastrin levels using a competitive radio immuno-assay and hepatic ME-DNA adduct levels using nuclease P1 enhanced 32P-postlabelling. Potential hepatic transcriptional changes mediated by ME were also investigated in animals of the high dietary dose group (50 mg/kg bw/day) compared to dietary controls, using a differential gene display PCR assay.No overt signs of dose-related toxicity were observed in any of the treatment groups, when bodyweights, liver weights, histopathology, haematology, blood chemistry and urinalysis were examined. Analysis of the PCNA levels in the four dose groups showed no significant difference from the control values. Comparison of appropriate post-study vehicle control plasma gastrin concentrations to corresponding post-study dose group values also showed no significant differences in male and female rats. However, ME-DNA adducts were detected in hepatic DNA from both male and female
AU - Ellis,JK
PY - 2008///
TI - Studies on the Molecular Basis of Methyl Eugenol Carcinogenicity
ER -