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.
Inano
Hiroshi
H
Redox Regulation Research Group, Research Center for Radiation Safety, National Institute of Radiological Sciences, Inage-ku, Chiba-shi, Japan. inano@nirs.go.jp
Onoda
Makoto
M
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D002273:Carcinogens; D003474:Curcumin / Q000494:pharmacology; D003497:Cyclic N-Oxides; D004054:Diethylstilbestrol; D002149:Energy Intake; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000517:prevention & control*; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control*; D009569:Nitric Oxide / Q000737:chemistry; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009589:Nitrogen Oxides / Q000494:pharmacology; D010052:Ovariectomy; D011837:Radiation-Protective Agents / Q000494:pharmacology; D019097:Spin Trapping
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D002273:Carcinogens; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; D011837:Radiation-Protective Agents; D009569:Nitric Oxide; C029217:phenyl-N-tert-butylnitrone; D004054:Diethylstilbestrol; D019001:Nitric Oxide Synthase; D003474:Curcumin