Immunotoxicity of Organic Arsenic Compounds in Marine Animals

Abstract

In the present study, we demonstrated for the first time the immunotoxic effects of organic arsenic compounds in marine animals, namely arsenocholine [AsCho; trimethyl(2‐hydroxyethyl)arsonium cation], arsenobetaine [AsBe; the trimethyl(carboxymethyl)arsonium zwitterion] and the tetramethylarsonium ion (TetMA), to murine principal immune effector cells (macrophages and lymphocytes), comparing them with the effects of inorganic arsenicals in vitro. Inorganic arsenicals (arsenite and arsenate) showed strong cytotoxicity to both macrophages and lymphocytes. The concentration of arsenite that reduced the number of surviving cells to 50% of that in untreated controls (IC50) was 3–5 μmol dm−3, and the cytotoxicity of arsenate (IC50=100 μ‐1 m mol dm−3) was lower than that of arsenite. Compared with these findings, trimethylarsenic compounds in marine animals, AsCho and AsBe, were less toxic even at a concentration over 10 mmol dm−3 to both macrophages and lymphocytes; however, TetMA had weak, but significant, cytotoxicity to these cells (IC50 was about 6 mmol dm−3).

Modulation of cell adhesion and viability of cultured murine bone marrow cells by arsenobetaine, a major organic arsenic compound in marine animals

“…However, an organic arsenic compound in marine animals, AsBe, was less toxic in thymocytes even at concentrations over 10 m M . Similar results were observed using PP lymphocytes; the percentage of the viability of PP lymphocytes incubated with 10 m M AsBe compared with that of control cells was 78.9±8.8%, and we previously reported that AsBe had no cytotoxicity in splenocytes even over 10 m M ( Sakurai et al ., 1996 ). These data imply that AsBe is less toxic in murine lymphocytes.…”

“…In contrast, using the synthesized pure material, we demonstrated that the toxicity of AsBe in mammals is very weak. First, we reported that AsBe had no acute toxicity when it was orally administered to mice ( Kaise et al ., 1985 ) and also described that AsBe was not toxic in vitro in murine macrophages and splenocytes even at concentrations over 10 m M ( Sakurai et al ., 1996 ). Thus, we had been believed that AsBe had no biological effects, including toxic effects, in mammals.…”

“…In this study, however, AsBe showed an interesting biological effect only on murine BM cells which are known to be very sensitive to changes of environmental conditions; AsBe significantly enhanced the cell viability of BM cells in vitro in a concentration‐dependent manner. AsBe was effective from a μ M level in BM cells (Figure 3), although it did not influence the other immune effector cells, such as thymocytes (Figure 2), PP lymphocytes, splenocytes and macrophages ( Sakurai et al ., 1996 ). The findings disclosed in this study represent the first report of a biological effect in mammalian cells of AsBe, a major organic arsenic compound in marine animals which are ingested daily as seafood in many countries.…”

“…Thymocytes (2.5×10 5 cells 100 μl −1 well −1 ) were incubated with arsenicals on flat‐bottomed 96‐well tissue culture plates for 72 h at 37°C in a CO 2 incubator in the presence of submitogenic concentrations of T cell mitogen, concanavalin A (Con A; Sigma; 2.5 μg ml −1 ), and the blastogenesis was determined by AB assay ( Sakurai et al ., 1996 ).…”

“…In 1985, our collaborator first reported the acute toxicity of AsBe using synthesized pure AsBe and found that it had no acute toxicity in murine models even over 10 g kg −1 when it was orally administered ( Kaise et al ., 1985 ). Subsequently, using this synthesized material we observed that the in vitro cytotoxicity of AsBe was very weak compared with that of inorganic arsenicals in cultured murine macrophages and splenocytes ( Sakurai et al ., 1996 ) additionally, AsBe did not induce chromosomal aberrations in human fibroblasts ( Oya‐Ohta et al ., 1996 ). Irvin & Irgolic (1988 ) also documented that AsBe had no embryotoxicity using rat models.…”