Cellular retention, toxicity and carcinogenic potential of seafood arsenic. I. Lack of cytotoxicity and transforming activity of arsenobetaine in the BALB/3T3 cell line

Abstract

Cytotoxicity, morphological neoplastic transformation, intracellular retention and metabolic behaviour have been investigated in BALB/3T3 CI A 31-1-1 cells for arsenobetaine, the main form of arsenic in certain seafoods, in comparison to inorganic sodium arsenite. In order to avoid false results, particular attention was paid to the purity, checking for the presence of any trace amounts of inorganic arsenic as well as methylated contaminants in the chemically synthesized arsenobetaine. Cytotoxicity and morphological transformation assays gave obvious positive results for sodium arsenite at a dose exposure of 10 µM. On the other hand, concentrations of arsenobetaine as high as 500 µM failed to induce either cytotoxic effects or neoplastic transformations. The absence of cytotoxicity and transforming potential of arsenobetaine in comparison to inorganic arsenite can be explained by the different degree of retention and the intracellular behaviour of the two arsenic species. Cellular retention of arsenobetaine was dose dependent for exposure concentrations ranging from 1 to 500 µM with a mechanism resembling a simple diffusion (1.4 and 760 pmol of As/10⁶ cells were cell associated for the two concentrations at 24 h respectively). About 95% of the intracellular arsenobetaine was present in the cytosol fraction and the attempt to detect any intracellular degradation of the organoarsenic compound failed. Thus, the low retention efficiency of arsenobetaine, its inability to interact with intracellular components and the absence of biotransformation in the cell could explain the lack of cytotoxicity and transforming potential observed in the BALB/3T3 cells. These findings reinforce the view that in humans exposed to different chemical species of arsenic the contribution to the total health risk, including the carcinogenic potential, of arsenobetaine ingested with marine foodstuffs would be negligible.