Tempol flexes chemopreventive muscle in preclinical study

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Supplements of the antioxidant Tempol in the diet of mice were able to safely reduce body weight, reduce or delay onset of cancer and extend survival, according to a study published in the Sept. 15 issue of Cancer Research.

The results of the preclinical study should warrant further research on the chemopreventive potential of Tempol, according to authors James B. Mitchell, of the National Cancer Institute in Behesda, Md., and colleagues.

Previous studies have shown that significant reductions in diet, amounting to between 25 percent and 40 percent cuts in calorie intake, can reduce incidence of cancer following exposure to ionizing radiation. The authors hypothesized that the administration of Tempol immediately following radiation exposure could mimic the effects of calorie restriction, which could greatly benefit exposed humans who would find it hard to make such dramatic changes in eating habits.

To test their hypothesis, Mitchell and colleagues tested the effect of chronic supplementation of Tempol in the diet of two strains of mice: female C3H/HenTac-MTV (C3H) and CBA/CaJ (CBA). “The data presented in this study clearly show that Tempol reduced the incidence of cancer post-TBI in C3H and CBA mice, thereby providing a significant survival advantage,” wrote the authors.

Both strains of mice demonstrated substantial reductions in lifespan of between 34 and 38 weeks after 3 Gy total body irradiation; however, Tempol diet supplementation immediately after exposure resulted in a significant survival advantage, according to the authors. CBA mice demonstrated an 18 week extension in survival when given Tempol and C3H mice showed a 34 week extension. C3H mice also had extended survival when Tempol supplementation was delayed one month post-radiation exposure.

“This latter finding is important in that it suggests that there may be a modifiable time threshold for [ionizing radiation]-induced life shortening,” wrote Mitchell and colleagues. They added that should the finding be shown in humans, it could mean that decisions to administer the antioxidant following an unexpected exposure to radiation—such as from a nuclear accident—could be made some time after the event once a proper dose assessment is conducted.

“The role of antioxidants as chemoprevention agents is controversial in that several clinical trials have shown no benefit of antioxidants in reducing or preventing carcinogenesis; however, preclinical studies, including this study, have shown that selected antioxidants, protease inhibitors, and dietary supplements can suppress certain [ionizing radiation]-induced cancers,” wrote the authors.