Fig. 2. Schematic drawing of the possible mechanism generating hydroxyl radicals and its role in heavy metalmediated carcinogenicity. tion metal ions, such as iron delivered by ferrocene (Fe(C5H5)2). Under the effect of ferrocene, hydrogen peroxide is split into hydroxyl anions and hydroxyl radicals, the latter of which induces apoptosis, leading to elimination of cancer cells. The hydroxyl radical is also free from residual toxicity because of its extremely short-half life, approximately 10−9 s.(7,8) In addition, hydrogen per- oxide, which was reported to be mutagenic and an intermediate able to generate hydroxyl radicals via a Fenton-like reaction in Cr- and arsenic-induced carcinogenicity,(12,16,28–30) is used in medical treatment for disinfection. Therefore, it is concluded that there is little to no risk of carcinogenicity as long as the hydroxyl radical is used as a disinfectant for short-term treatment of the oral cavity as reported in our previous study.(1) References 1 Ikai H, Nakamura K, Shirato M, et al. Photolysis of hydrogen peroxide, an effective disinfection system via hydroxyl radical formation. Antimicrob Agents Chemother 2010; 54: 5086–5091. 2 Iwasawa A, Saito K, Mokudai T, Kohno M, Ozawa T, Niwano Y. Fungicidal action of hydroxyl radicals generated by ultrasound in water. J Clin Biochem Nutr 2009; 45: 214–218. 3 Kohno M, Mokudai T, Ozawa T, Niwano Y. Free radical formation from sonolysis of water in the presence of different gases. J Clin Biochem Nutr 2011; 49: 96–101. 4 Darley-Usmar V, Halliwell B. Blood radicals: reactive nitrogen species, reac- tive oxygen species, transition metal ions, and the vascular system. Pharm Res 1996; 13: 649–662. 5 Halliwell B. Free radicals, proteins and DNA: oxidative damage versus redox T. Kanno et al. Abbreviations AP-1 Cr DMPO DMSO ESR F-12 NF-κB p-AP PMA PMN ROS SOD activator protein-1 chromium 5,5-dimethyl-1-pyrroline-N-oxide dimethyl sulfoxide electron spin resonance fecapentaene-12 nuclear factor-κB p-aminophenol phorbol-12-acetate-13-myristate polymorphonuclear leukocyte reactive oxygen species superoxide dismutase regulation. Biochem Soc Trans 1996; 24: 1023–1027. 6 Halliwell B. Oxidative stress, nutrition and health. Experimental strategies for optimization of nutritional antioxidant intake in humans. Free Radic Res 1996; 25: 57–74. 7 Pryor WA. Oxy-radicals and related species: their formation, lifetimes, and reactions. Annu Rev Physiol 1986; 48: 657–667. 8 Sies H, Stahl W, Sundquist AR. Antioxidant functions of vitamins. Vitamins E and C, beta-carotene, and other carotenoids. Ann NY Acad Sci 1992; 669: 7– 20. 9 de Kok TM, van Maanen JM, Lankelma J, ten Hoor F, Kleinjans JC. Electron spin resonance spectroscopy of oxygen radicals generated by synthetic fecapentaene-12 and reduction of fecapentaene mutagenicity to Salmonella typhimurium by hydroxyl radical scavenging. Carcinogenesis 1992; 13: J. Clin. Biochem. Nutr. | July 2012 | vol. 51 | no. 1 | 13 ©2012 JCBN