title: Mitigation of radiation-induced dermatitis by activation of aldehyde dehydrogenase 2 using topical alda-1 in mice.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Stanford University Medical Center, Stanford, California 94305, USA.
authors.forename: Shoucheng
authors.initials: S
authors.lastname: Ning
authors.forename: Grant R
authors.initials: GR
authors.lastname: Budas
authors.forename: Eric N
authors.initials: EN
authors.lastname: Churchill
authors.forename: Che-Hong
authors.initials: CH
authors.lastname: Chen
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Knox
authors.forename: Daria
authors.initials: D
authors.lastname: Mochly-Rosen
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D052117:Benzodioxoles / Q000008:administration & dosage / Q000494:pharmacology*; D004789:Enzyme Activation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011855:Radiodermatitis / Q000188:drug therapy* / Q000201:enzymology; D012867:Skin / Q000201:enzymology / Q000473:pathology
chemical_list: D000447:Aldehydes; D001549:Benzamides; D052117:Benzodioxoles; C531525:N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide; C515029:ALDH2 protein, mouse; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C027576:4-hydroxy-2-nonenal