Monomethylarsonous acid: Induction of DNA damage and oxidative stress in mouse natural killer cells at environmentally-relevant concentrations

Abstract

The carcinogenicity of arsenic has been confirmed in many studies, but its mechanism of action is still unclear. A lymphocyte component of the innate immune system, natural killer (NK) cells are responsible for killing cancer cells. Although inorganic arsenical species are the prevalent forms of arsenic in the environment, monomethylarsonous acid (MMA⁺³) is the major arsenical species found in immune-system cells, in this 30 d drinking-water-exposure study in mice. Therefore, the effect of MMA⁺³ on NK cells should be studied as a possible contributor to arsenic-induced toxicity at environmental exposure levels. In the mouse drinking-water-exposure model, As⁺³ induces dose-dependent DNA damage in NK cells. In in vitro studies, MMA⁺³ inhibited cell growth and induced DNA damage and oxidative stress at low concentration (20 and 50 nM) in isolated mouse NK cells. Strong correlations were found between DNA damage and oxidative stress in MMA⁺³-treated mouse NK cells. Even at low concentrations relevant to environmental arsenic exposures, MMA⁺³ is genotoxic to primary mouse NK cells.

Keywords: Arsenic; Carcinogenesis; Genotoxicity; Monomethylarsonous acid; Nature killer cells; Oxidative stress.