n-(1-3-benzodioxol-5-ylmethyl)-2-6-dichlorobenzamide and Radiodermatitis

Radiation-induced dermatitis is a debilitating clinical problem in cancer patients undergoing cancer radiation therapy. It is also a possible outcome of exposure to high levels of radiation due to accident or hostile activity. We report that activation of aldehyde dehydrogenase 2 (ALDH2) enzymatic activity using the allosteric agonist, Alda-1, significantly reduced 4-hydroxynonenal adducts accumulation, delayed the onset of radiation dermatitis and substantially reduced symptoms in a clinically-relevant model of radiation-induced dermatitis. Importantly, Alda-1 did not radioprotect tumors in mice. Rather, it increased the sensitivity of the tumors to radiation therapy. This is the first report of reactive aldehydes playing a role in the intrinsic radiosensitivity of normal and tumor tissues. Our findings suggest that ALDH2 represents a novel target for the treatment of radiation dermatitis without reducing the benefit of radiotherapy.

Topics: Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Aldehydes; Animals; Benzamides; Benzodioxoles; Enzyme Activation; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Radiodermatitis; Skin