17beta-estradiol acting as an electron mediator: experiments in vitro.
BACKGROUND
The present work reports on the effect of oxidizing (OH, O(2)(*-)) and reducing free radicals (e(-)(aq), H) on 17beta-estradiol (17betaE2) in respect to breast cancer initiation. The objectives of the study were based on the following premise: the ability of 17betaE2 to emit electrons (e(-)(aq)) as well as to transfer them to other biological systems. Thereby, the resulting transient hormone products are leading to the formation of metabolites, some of which may initiate the neoplastic process. The present work considers the effect of the simultaneously generated oxidizing and reducing free radicals on the carcinogenic properties of the 17betaE2 metabolites.


METHODS
Water-soluble 17betaE2 with incorporated 2-hydroxypropyl-beta-cyclodextrin (HBC) in various aqueous media (pH ~7.4), saturated with air, N(2)O or argon, as well as HBC alone, were exposed to the action of free radicals produced by gamma-ray. Escherichia coli bacteria (AB 1157) were used as a model for living systems.


RESULTS
From the survival curves obtained under different conditions, the derived DeltaD(37) values (representing the radiation dose at which N/N(0)=0.37; N/N(0) ratio: N(0)=starting number of colonies, N=number after irradiation treatment) illustrate that 17betaE2 as well as HBC act as very powerful scavengers of OH and O(2)(*-) radicals. On the other hand, 17betaE2 and HBC intermediates resulting from attack of the reducing species (e(-)(aq), H) have strong anticancer properties.


CONCLUSIONS
It is stated that DeltaD(37) values strongly depend on the reactivity of the individual free radicals. Oxidizing free radicals lead to positive DeltaD(37) values, illustrating the strongly pronounced radiation protecting ability of the systems. On the contrary, the primary reducing free radicals result in negative DeltaD(37) values, indicating anticancer effect.
Getoff
Nikola
N
Section of Radiation Biology, Faculty of Life Sciences, University of Vienna, A-1090 Vienna, Austria. nikola.getoff@univie.ac.at
Schittl
Heike
H
Gerschpacher
Marion
M
Hartmann
Johannes
J
Huber
Johannes C
JC
Quint
Ruth-Maria
RM
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D004583:Electrons; D004926:Escherichia coli / Q000254:growth & development / Q000378:metabolism* / Q000528:radiation effects; D004958:Estradiol / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D005079:Excipients / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010084:Oxidation-Reduction / Q000528:radiation effects; D014867:Water / Q000737:chemistry / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000378:metabolism
D005079:Excipients; D005609:Free Radicals; D047392:beta-Cyclodextrins; D014867:Water; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D004958:Estradiol