Effects of Systemic or Topical Administration of Sodium Selenite on Early Radiation Effects in Mouse Oral Mucosa

Abstract

Administration of sodium selenite during clinically relevant fractionated irradiation protocols has a significant effect during the initial treatment phase, i.e., week 1 in the mouse. Therefore, in clinical radiotherapy, the latent time to manifestation of confluent mucositis may be significantly prolonged, and hence the burden for the patient clearly reduced by selenium.

Effects of Selenium on Radiation Responses of Tumor Cells and Tissue

“…By contrast, most squamous cell carcinomas display acceleration of repopulation during radiotherapy [2,19,20,26]. A shortening of the lag phase before the onset of radiation-induced repopulation, however, was suggested as one potential mechanism of the protective effect of selenium in oral mucosa [9]. If such an effect were present in tumors, it could not have been depicted in the studies with the R1H tumor.…”

“…For local administration of selenium, e.g., as a mouthwash to reduce oral mucositis [9], this may be of less importance, but may be relevant for systemic administration. Therefore, well-designed and detailed studies, with relevant animal models, e.g., squamous cell carcinoma xenografts, and with clinically relevant fractionation protocols over several weeks, are recommended.…”

“…Activation or stimulation of this enzymatic system is supposed to reduce the amount of toxic oxygen compounds in the irradiated cells. A significant effect of selenium has recently been demonstrated for radiation-induced oral mucositis in a preclinical study [9], and the authors concluded that a clinical study would be required to confirm their results.…”

Normal-Tissue Radioprotection by Overexpression of the Copper-Zinc and Manganese Superoxide Dismutase Genes

“…Therefore, new approaches that can increase the therapeutic window are imperative. This may be accomplished by increasing the radioresistance of the normal tissue without protecting the tumor cells (examples of approaches: application of sodium selenite [10], proteolytic enzymes [3] or amifostine [13,27] during radiotherapy).…”

Selenium Levels during the Course of Radiotherapy

“…Also since the 1960s a radioprotective effect of selenium compounds has been found in vitro and in vivo [5,31]. Intriguingly, not only a potential in the prevention of radio-or chemotherapy-induced toxicity [9,13,24,26,27], but also a potential in enhancement of antitumor activity has been suggested in some studies [8,10,12,15,29]. Recent clinical trials suggested the blood selenium concentration as predictor for tumor activity, treatment response, and overall survival: in patients with aggressive non-Hodgkin's lymphoma, serum selenium at presentation was predicting positively for dose delivery, treatment response, and long-time survival [19] and in patients with advanced head-and-neck cancer, a correlation between selenium concentration and tumor resectability was found [6].…”