Carcinogenesis, Vol 19, 437-443, Copyright © 1998 by Oxford University Press
WJ Bodell, Q Ye, DN Pathak and K Pongracz
We have investigated the activation of eugenol to form DNA adducts and
oxidative base damage. Treatment of myeloperoxidase containing HL-60 cells
with eugenol, produced a dose-dependent formation of three DNA adducts as
detected with P1-enhanced 32P-post-labeling. Incubation of HL-60 cells with
the combination of 100 microM eugenol and 100 microM H2O2 potentiated the
levels of DNA adduct in HL-60 cells by 14-fold, which suggests peroxidase
activation in adduct formation. In vitro activation of eugenol with either
horseradish peroxidase or myeloperoxidase and H2O2 produced three DNA
adducts that were inhibited by the addition of either ascorbic acid or
glutathione, by 66 and 90%, respectively. The DNA adducts formed in HL-60
cells treated with eugenol were the same as those formed by in vitro
peroxidase activation. In addition to adduct formation, peroxidase
activation of eugenol produced a 2- to 3-fold increase in the level of
oxidative base damage. Eugenol quinone methide was prepared by Ag(I)oxide
oxidation of eugenol. Peroxidase activation of eugenol gave a product that
had the same UV spectrum as eugenol quinone methide, which suggests that it
was one of the products. Reaction of eugenol quinone methide with either
DNA or deoxyguanosine-3'-phosphate produced two principal adducts (2 and
4). When DNA adduct 2 formed by incubation of eugenol quinone methide with
deoxyguanosine-3'-phosphate was compared with DNA 2 adduct formed in HL-60
cells treated with eugenol results demonstrated that they were the same.
This suggests that eugenol quinone methide is one of the reactive
intermediates leading to DNA adduct formation in cells. Activation of
eugenol with 10 microM copper sulfate resulted in the production of one
principal (2) and several minor adducts. DNA adduct 2 formed by activation
of eugenol with copper sulfate was the same as DNA adduct 2 formed by
either peroxidase activation of eugenol or by reactions with eugenol
quinone methide, which indicates that the reactive intermediates generated
by these activation systems were similar. Copper sulfate produced a 95-fold
increase in the level of oxidative base damage, which was significantly
inhibited by the addition of either bathocuproinedisulphonic acid or
catalase. The formation of oxidative base damage was consistent with a
Fenton reaction mechanism. Our results demonstrate that eugenol can be
activated to form both DNA adducts and oxidative base damage. We propose
that the formation of this DNA damage may contribute to the observed toxic
properties of eugenol.
ARTICLES
Oxidation of eugenol to form DNA adducts and 8-hydroxy-2'- deoxyguanosine: role of quinone methide derivative in DNA adduct formation
Brain Tumor Research Center, Department of Neurological Surgery, University of California, San Francisco 94143-0806, USA. bodell@itsa.ucsf.edu
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