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ABSTRACT: Prevention of radiation-induced mammary tumors
The radiation-induced rat mammary tumor model is useful for
studying tumor prevention by treatment in the initiation or
promotion stage. In anti-initiation experiments, the
administration of radical scavengers or spin-trapping agents
before or immediately after irradiation reduced the incidence
of mammary tumors, suggesting that free radicals produced by
exposure are a potent initiator.
To evaluate the role of
nitric oxide (NO) in the initiation, NO-specific scavengers
or NO synthase inhibitors were administered during the initiation.
These agents partially prevented the tumorigenesis, suggesting
that radiation-induced NO contributes to tumor initiation.
The administration of curcumin during irradiation reduced the
incidence of the tumors in the presence of tumor promotor. In
anti-promotion experiments on preventing diethylstilbestrol
(DES)-dependent tumor development from mammary primodial cells
exposed to radiation, tamoxifen decreased the tumor incidence.
From the results, estrogen itself or prolactin induced by
estrogen may be a promoter for the tumorigenesis. Bezafibrate
and simvastatin, agents inducing hypolipidemia and hypocholesterolemia
respectively, cause a decrease in the DES-dependent promotion of
radiation-induced tumorigenesis.
The simultaneous administration
of curcumin and DES significantly reduces the development of
mammary tumors in irradiated rats.
In this review, the
endocrinologic and pharmacologic significance of the anti-initiation
and anti-promotion is discussed.
[01/10/2002; International Journal of Radiation Oncology, Biology, Physics]
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