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tent with the potentiometric data. Spectroscopic studies
indicate that the ME2’s and HME2’s were inert toward
the LP-catalyzed oxidation by peroxide.
Thus, both the 2- and 4-HE2’s are capable of causing
significant DNA damage at high micromolar concentra-
tions while in the presence of Cu(II) in vitro. Although
copper concentrations have been reported to reach into
the micromolar range under some circumstances (31, 32),
the concentrations of CE’s have not been shown to
surpass sub-nanomolar levels in serum (5). Furthermore,
serum estradiol concentrations equal to or less than
approximately 2.5 ng/mL are sufficient to induce tum-
origenesis in vivo in the ACI rat mammary tumor model
and the Syrian hamster kidney tumor model (36, 37),
suggesting that concentrations of CE metabolites are
below nanomolar levels. In addition, considerations for
many cellular defenses such as conjugating enzymes,
DNA binding proteins, and DNA repair have not been
addressed in this paper. However, SOD, catalase, and
GSH all suppressed 8-oxo-dG formation significantly in
the presence of 100 µM 2-HE2 and 100 µM Cu(II)SO4.
Taken as a whole, it is unlikely that free radical produc-
tion via redox cycling of CE’s is a causative factor in
human tumorigenesis. The HME2’s were shown to be
stable analogues of the HE2’s and should prove to be
useful probes in the study of receptor-mediated carcino-
genesis. Extension of this study to an ER positive breast
cancer cell model is underway.
Ack n ow led gm en t. This research is supported by
NIH Grants T32 CA09498, R21 CA66193, R01 CA73698,
and P30 CA16058 and U.S. AMRMC Grant DAMD17-
96-1-6136. Special thanks to Dr. Larry Cain for use of
the potentiometric equipment and for advice regarding
the electrochemical studies.
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