Biological availability of nickel arsenides: Cellular response to soluble Ni5As2

Abstract

Particulate Ni5As2 has been shown to be highly cytotoxic and carcinogenic. By measuring the solubility of Ni5As2 particles in a variety of aqueous solutions, we have determined that particulate Ni5As2 that might be produced during oil-shale retorting could be mobilized to the environment and made available to the cells of living organisms, including humans. Ni5As2 was five times more soluble in ground water taken from aquifers surrounding a major oil-shale source in Colorado, U.S.A., than in distilled water. It was also two times more soluble in oil-shale product water from an above-ground retort than in distilled water. Thus, it is possible that Ni5As2 could be solubilized and mobilized to the environment by the flooding of abandoned in situ retorts with ground water or by the disposal of oil-shale product water by spraying it on spent shale beds. Particulate Ni5As2 was found to be 12 times more soluble in culture growth medium than in distilled water, and much more soluble in solutions of amino acids, inorganic salts, organic constituents of culture medium, and 15% calf serum. These observations suggest Ni5As2 particles in airborne dust would be dissolved when they came in contact with the biological fluids of the lung and gastrointestinal tract. The availability to cells of the soluble products of Ni5As2 was demonstrated by measuring its effects on cell proliferation. As little as 1 ppm soluble Ni5As2 retarded Chinese hamster (CHO) cell proliferation in culture, and 4 ppm resulted in cell death. Flow cytometry measurements indicated there was a preferential cytotoxic effect on S-phase cells. Despite this, many cells survived to form colonies, causing concern that Ni5As2 might cause genetic damage that could be passed on to future cell generations. This did not appear to be the case, however, for no mutations could be detected at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in cells that survived the cytotoxic effects. This suggests that Ni5As2 carcinogenesis might be caused by epigenetic rather than mutagenic mechanisms.

Arsenic[III] and heavy metal ions induce intrachromosomal homologous recombination in thehprt gene of V79 Chinese hamster cells

“…Our findings indicate that inorganic arsenic induces homologous recombination, with retention of the downstream copy of exon 7 of the hprt gene in the SPD8 cell line, which is consistent with the involvement of a chromatid exchange mechanism. In light of previous observations that cells in the S-phase are most sensitive to the cytotoxicity of arsenic [Gurley et al, 1986], which also arrests cells in this phase [Peters et al, 1976;Yager and Wiencke, 1997], the enhanced recombination frequency observed here may be related to inhibition of DNA replication and the subsequent formation of strand breaks. The homologous recombination induced by Cobalt[II] is probably related to its clastogenic ability to induce DNA strand breaks and chromosomal aberrations, as well as SCEs [Hartwig, 1995].…”