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Charles O. Abernathy,¹ Yung-Pin Liu,² David Longfellow,² H. Vasken Aposhian,³ Barbara Beck,⁴ Bruce Fowler,⁵ Robert Goyer,⁶ Robert Menzer,¹ Toby Rossman,⁷ Claudia Thompson,⁸ and Michael Waalkes⁹

¹Offices of Water and Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA
²Division of Cancer Biology, National Cancer Institute, Bethesda, Maryland, USA
³University of Arizona, Tucson, Arizona, USA
⁴Gradient Corporation, Cambridge, Massachusetts, USA
⁵University of Maryland Baltimore County, Catonsville, Maryland, USA
⁶Chapel Hill, North Carolina, USA
⁷New York University Medical Center, Tuxedo, New York, USA
⁸National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA
⁹Inorganic Carcinogenesis Section, National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA

Abstract

A meeting on the health effects of arsenic (As) , its modes of action, and areas in need of future research was held in Hunt Valley, Maryland, on 22-24 September 1997. Exposure to As in drinking water has been associated with the development of skin and internal cancers and noncarcinogenic effects such as diabetes, peripheral neuropathy, and cardiovascular diseases. There is little data on specific mechanism(s) of action for As, but a great deal of information on possible modes of action. Although arsenite [As(III) ] can inhibit more than 200 enzymes, events underlying the induction of the noncarcinogenic effects of As are not understood. With respect to carcinogenicity, As can affect DNA repair, methylation of DNA, and increase radical formation and activation of the protooncogene c-myc, but none of these potential pathways have widespread acceptance as the principal etiologic event. In addition, there are no accepted models for the study of As-induced carcinogenesis. At the final meeting session we considered research needs. Among the most important areas cited were a) As metabolism and its interaction with cellular constituents ; b) possible bioaccumulation of As ; c) interactions with other metals ; d) effects of As on genetic material ; e) development of animal models and cell systems to study effects of As ; and f) a better characterization of human exposures as related to health risks. Some of the barriers to the advancement of As research included an apparent lack of interest in the United States on As research ; lack of relevant animal models ; difficulty with adoption of uniform methodologies ; lack of accepted biomarkers ; and the need for a central storage repository for stored specimens. Key words: S-adenosylmethionine, arsenic, arsenate, aresenite, dimethylarsinic acid, heat shock proteins, heme oxygenase, monomethylarsonic acid. Environ Health Perspect 107:593-597 (1999) . [Online 14 June 1999]

http://ehpnet1.niehs.nih.gov/docs/1999/107p593-597abernathy/ abstract.html

Address correspondence to C.O. Abernathy, Office of Science and Technology (4304) , Room 1037 East Tower, 401 M Street, SW, Washington, DC, USA 20460-0001. Telephone: (202) 260-5374. Fax: (202) 260-1036. E-mail: abernathy.charles@epa.gov

This conference was supported by the National Cancer Institute, Bethesda, MD ; the U.S. Environmental Protection Agency, Washington, DC ; and the National Institute of Environmental Health Sciences, Research Triangle Park, NC.

The views expressed in this report are those of the authors and do not necessarily reflect the policies or opinions of the U.S. Environmental Protection Agency, the National Cancer Institute, or the National Institute of Environmental Health Sciences.

Received 17 December 1998 ; accepted 22 March 1999.