Arsenite Interacts with Dibenzo[def,p]chrysene (DBC) at Low Levels to Suppress Bone Marrow Lymphoid Progenitors in Mice

Abstract

Arsenite (As⁺³) and dibenzo[def,p]chrysene (DBC), a polycyclic aromatic hyrdrocarbon (PAH), are found in nature as environmental contaminants. Both are known to individually suppress the immune system of humans and mice. In order to determine their potential interactive and combined immunosuppressive effects, we examined murine bone marrow (BM) immune progenitor cells’ responses following combined oral exposures at very low levels of exposure to As⁺³ and DBC. Oral 5-day exposure to DBC at 1 mg/kg (cumulative dose) was found to suppress mouse BM lymphoid progenitor cells, but not the myeloid progenitors. Previously established no-effect doses of As⁺³ in drinking water (19 and 75 ppb for 30 days) produced more lymphoid suppression in the bone marrow when mice were concomitantly fed a low dose of DBC during the last 5 days. The lower dose (19 ppb) As⁺³ had a stronger suppressive effect with DBC than the higher dose (75 ppb). Thus, the interactive toxicity of As⁺³ and DBC in vivo could be As⁺³ dose dependent. In vitro, the suppressive interaction of As⁺³ and DBC was also evident at low concentrations (0.5 nM), but not at higher concentrations (5 nM) of As⁺³. These studies show potentially important interactions between As⁺³ and DBC on mouse BM at extremely low levels of exposure in vivo and in vitro.