In vitro cyto-toxic assessment of heavy metals and their binary mixtures on mast cell-like, rat basophilic leukemia (RBL-2H3) cells

We investigated the cytotoxicity and mechanisms of cell death induced by salts of Cadmium (Cd²⁺), Lead (Pb²⁺), Arsenic (AsO₄^3-) and Chromium (Cr⁺⁶) on RBL-2H3 cells (a model mast cell line). In addition, cyto-toxic effect on cell viability was assessed to reveal their nature of interaction in binary mixture. The individual cytotoxic characteristics of these metals on RBL-2H3 cell viability showed a concentration-dependent reduction of cell viability. We observed that concentration-dependent cytotoxic potency on RBL-2H3 cells of these metals range in the following order Cd²⁺>Cr⁺⁶>As O₄^3- > Pb²⁺ with LC₅₀ values of 0.11 μM, 93.58 μM, 397.9 μM and 485.3 μM respectively. Additive effects were observed with Pb²⁺ + Cd²⁺, Pb²⁺ + AsO₄^3-, Pb²⁺ + Cr⁺⁶ and AsO₄^3- + Cr⁺⁶. The study revealed that Pb²⁺, Cd²⁺, AsO₄^3- and Cr⁺⁶ could induce significant (P < 0.01) cell death by apoptosis in RBL-2H3. Highly significant necrotic cell death was observed with Pb²⁺ and Cr⁺⁶ (P < 0.01) than Cd²⁺ and AsO₄^3- (P < 0.05). Overall, it can be deduced that several cell death executing pathways may be concomitantly activated on exposure to heavy metals and the predominance of one over others might depend on the type of heavy metal, concentration and the metabolic state of the cell. Eventually, binary mixtures of some of these metals showed less cytotoxicity than would be expected from their individual actions and may depend on the co-exposure of the metal ions and their modes of action.