| Mechanism of Selenium-Induced Inhibition of Arsenic-Enhanced UVR Carcinogenesis in Mice Fredric J. Burns,1 Toby Rossman,1 Katherine Vega,1 Ahmed Uddin,1 Stefan Vogt,2 Barry Lai,2 and Richard J. Reeder3 1Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, USA; 2Experimental Facilities Division, Advanced Photon Source, Argonne National Laboratory, Argonne, Illinois, USA; 3Department of Geosciences, Center for Environmental Molecular Science, State University of New York at Stony Brook, Stony Brook, New York, USA Abstract
Background: Hairless mice that ingested arsenite in drinking water exhibited more than a 5-fold enhancement of ultraviolet radiation (UVR) carcinogenesis, whereas arsenite alone was carcinogenically inactive. Dietary organoselenium blocked the cancer enhancement effect of arsenic but not cancer induction by UVR. Objective: In this study we sought to explain selenium blockage of As enhancement by establishing the extent that As and Se tissue distributions are coincident or divergent. Methods: We used the X-ray fluorescence microprobe at the Advanced Photon Source (Argonne National Laboratory) to probe sections of skin and liver from hairless mice exposed to a) UVR, b) UVR + As, c) UVR + organoselenium, or d) UVR + As + organoselenium. Results: We found elevated levels of As in the skin epithelium (hair follicles and epidermis) and diffusely in the liver of mice exposed to UVR + As. Arsenic was entirely absent in skin in mice exposed to UVR + As + organoselenium, but a diffuse low level was seen in the liver. As and Se locations were consistently divergent in skin ; As was more diffusely distributed, whereas Se was strongly associated with membranes. X-ray absorption near-edge spectra are consistent with the presence of the seleno-bis(S-glutathionyl) arsinium ion in the liver. Conclusions: Supplemental Se was uncommonly effective at preventing even a trace of As in skin at 14 or 196 days of continuous exposure to As in drinking water. Traces of the seleno-bis(S-glutathionyl) arsinium ion in the liver suggested that formation of this compound was more likely to be responsible for the As-blocking effect of Se than was a mechanism based on antioxidation. Key words: arsenic, cancer, mouse, prevention, radiation, selenium, skin, ultraviolet, UVR. Environ Health Perspect 116:703–708 (2008) . doi:10.1289/ehp.10978 available via http://dx.doi.org/ [Online 1 February 2008]
Address correspondence to F.J. Burns, New York University School of Medicine, Department of Environmental Medicine, 57 Old Forge Rd., Tuxedo, NY 10987 USA. Telephone: (845) 731-3551. Fax: (845) 351-5472. E-mail: burns@env.med.nyu.edu This work was supported by NASA grant NAG9-1528, National Cancer Institute Center grant CA16087 (New York University Kaplan Cancer Center) , and National Institute of Environmental Health Science Center grant ES00260 (Nelson Institute of New York University) . The Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under contract DE-AC02-06CH11357. The authors declare they have no competing financial interests. Received 12 October 2007 ; accepted 1 February 2008.
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