Mechanism of selenium-induced inhibition of arsenic-enhanced UVR carcinogenesis in mice.
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.
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA. burns@env.med.nyu.edu
Fredric J
FJ
Burns
Toby
T
Rossman
Katherine
K
Vega
Ahmed
A
Uddin
Stefan
S
Vogt
Barry
B
Lai
Richard J
RJ
Reeder
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001151:Arsenic / Q000633:toxicity*; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D016566:Organoselenium Compounds / Q000494:pharmacology; D012643:Selenium / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D013052:Spectrometry, X-Ray Emission; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000970:Antineoplastic Agents; D016566:Organoselenium Compounds; D012643:Selenium; D001151:Arsenic