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Carcinogenesis Advance Access published online on July 13, 2005
Carcinogenesis, doi:10.1093/carcin/bgi180
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oupjournals.org
Received March 30, 2005
Revised June 29, 2005
Accepted July 4, 2005

CARCINOGENESIS

Vitamin E and organoselenium prevent the cocarcinogenic activity of arsenite with solar UV in mouse skin

Ahmed N. Uddin 1, Fredric J. Burns 1, and Toby G. Rossman 1*

1 Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA

* To whom correspondence should be addressed.
Toby G. Rossman, E-mail: rossman{at}env.med.nyu.edu


  Abstract

Arsenic-induced carcinogenesis is a worldwide problem for which there is currently limited means for control. Recently, we showed that arsenite in drinking water greatly potentiates solar ultraviolet radiation (UVR) induced skin cancer in mice at concentrations as low as 1.25 mg/l. In this study, we examined the protective efficacy of vitamin E and 1,4-phenylenebis(methylene)selenocyanate (p-XSC) against tumors induced by UVR and UVR + arsenite. Hairless mice were exposed to UVR alone (1.0 kJ/m2 x 3 times weekly) or UVR + sodium arsenite (5 mg/l in drinking water) and fed lab chow supplemented or not with vitamin E (RRR-{alpha}-tocopheryl acetate, 62.5 IU/kg diet) or p-XSC (10 mg/kg) for 26 weeks. The tumor yield for mice receiving UVR alone was 3.6 tumors/mouse and the addition of arsenite to the drinking water increased the yield to 7.0 tumors/mouse (p<0.005). Vitamin E and p-XSC reduced the tumor yield in mice given UVR + arsenite by 2.1-fold (p<0.001) and 2-fold (p<0.002), respectively. Vitamin E, but not p-XSC, reduced the tumor yield induced by UVR alone by 30% (p<0.05). No significant difference in tumor types or grade of malignancy was observed in mice treated with or without chemopreventives. Immunostaining of mouse skin for 8-oxo-2'-deoxyguanosine (8-oxo-dG) revealed a significant reduction of 8-oxo-dG formation in mice treated with vitamin E or p-XSC compared with those treated with UVR + arsenite. These results show that vitamin E and p-XSC protects strongly against arsenite-induced enhancement of UVR carcinogenesis.

Keywords: Skin; cancer; prevention; solar UV; arsenic; vitamin E; selenium; mouse.

Authors are listed in the order of their contribution to the work


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