Toxicity of inorganic arsenic and its metabolites on haematopoietic progenitors ¿in vitro¿: comparison between species and sexes.

Abstract Inorganic arsenic (iAs) and its metabolites are transferred to the foetus through the placental barrier and this exposure can compromise the normal development of the unborn. For this reason, we assessed the toxicity of sodium arsenite (iAs III ) and its metabolites dimethylarsinic acid (DMA V ), monomethylarsonic acid (MMA V ) and monomethylarsonous acid (MMA III ) on human haematopoietic cord blood cells and murine bone marrow progenitors in vitro , looking at the effects induced at different concentrations in the two genders. The expression of two enzymes responsible for arsenic biotransformation arsenic methyltranferase (AS3MT) and glutathione S -transferase omega 1 (GSTO1) was evaluated in human cord blood cells. Cord blood and bone marrow cells were exposed in vitro to iAs III at a wide range of concentrations: from 0.0001 μM to 10 μM. The methylated arsenic metabolites were tested only on human cord blood cells at concentrations ranging from 0.00064 μM to 50 μM. The results showed that iAs III was toxic on male and female colony forming units to about the same extent both in human and in mouse. Surprisingly, very low concentrations of iAs III increased the proliferation rate of both human and murine female cells, while male cells showed no significant modulation. MMA V and DMA V did not exert detectable toxicity on the cord blood cells, while MMA III had a marked toxic effect both in male and female human progenitors. AS3MT mRNA expression was not induced in human cord blood cells after iAs III exposure. GSTO1 expression decreased after MMA III treatment. This study provides evidence that exposure to iAs III and MMA III at μM concentrations is associated with immunosuppression in vitro .