Authors: Ding, Wei¹; Hudson, Laurie¹; Liu, Ke²

Source: Molecular and Cellular Biochemistry, Volume 279, Numbers 1-2, November 2005 , pp. 105-112(8)

Publisher: Springer

Abstract:

Arsenic is a naturally occurring element that is present in food, soil, and water. Inorganic arsenic can accumulate in human skin and is associated with increased risk of skin cancer. Oxidative stress due to arsenic exposure is proposed as one potential mode of carcinogenic action. The purpose of this study is to investigate the specific reactive oxygen and nitrogen species that are responsible for the arsenic-induced oxidative damage to DNA and protein. Our results demonstrated that exposure of human keratinocytes to trivalent arsenite caused the generation of 8-hydroxyl-2′-deoxyguanine (8-OHdG) and 3-nitrotyrosine (3-NT) in a concentration- and time-dependent manner. Pentavalent arsenate had similar effects, but to a significantly less extent. The observed oxidative damage can be suppressed by pre-treating cells with specific antioxidants. Furthermore, we found that pre-treating cells with Nω-nitro-l-arginine methyl ester (l-NAME), an inhibitor of nitric oxide synthase (NOS), or with 5,10,15,20-tetrakis (N-methyl-4′-pyridyl) porphinato iron (III) chloride (FeTMPyP), a decomposition catalyst of peroxynitrite, suppressed the generation of both 8-OHdG and 3-NT, which indicated that peroxynitrite, a product of the reaction of nitric oxide and superoxide, played an important role in arsenic-induced oxidative damage to both DNA and protein. These findings highlight the involvement of peroxynitrite in the molecular mechanism underlying arsenic-induced human skin carcinogenesis.

Keywords: arsenic; DNA damage; keratinocytes; oxidative stress

Document Type: Research article

DOI: http://dx.doi.org/10.1007/s11010-005-8227-y

Affiliations: 1: Program of Toxicology, College of Pharmacy, University of New Mexico Health Science Center, Albuquerque, NM, 87131, USA, 2: Program of Toxicology, College of Pharmacy, University of New Mexico Health Science Center, Albuquerque, NM, 87131, USA, Email: jliu@unm.edu

Publication date: 2005-11-01

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