Chromium(III) tris(picolinate) is mutagenic at the hypoxanthine (guanine) phosphoribosyltransferase locus in Chinese hamster ovary cells

Abstract

Chromium trispicolinate (CrPic) is a popular dietary supplement that is not regulated by the Food and Drug Administration. We are using this compound as a bio-available model to explore the role of Cr(III) in Cr(VI)-induced cancers. The ability of CrPic to cause mutations at the hypoxanthine (guanine) phosphoribosyltransferase (hprt) locus of CHO AA8 cells has been measured after a 48 h exposure. The highest dose tested was 80 microg/cm(2) CrPic, which, if fully soluble, would be equivalent to 1mM or 0.44 mg/ml CrPic, and would correspond to 1mM Cr(III) or 52 microg/ml Cr(III). This exposure resulted in 68+/-16% cell survival based on 48 h cell counts, and 24+/-11% survival by 7-day colony formation. Exposure of CHO cells to CrPic produced a statistically significant increase in 6-thioguanine (6-TG)-resistant cells over the dose range tested. The 80 microg/cm(2) CrPic exposure resulted in an average induced mutation frequency (MF) of 58 per 10(6) surviving cells, or an average 40-fold increase in hprt mutants relative to untreated cells. An equivalent dose of 3mM Pic was highly cytotoxic and did not yield hprt mutants. The dose range of 0.375-1.5mM Pic produced a slight increase in hprt mutants, but the increase was not statistically significant. An equivalent dose of 1mM chromic chloride yielded an induced MF of 9 per 10(6) surviving cells, or a 10-fold increase in mutants with cell survivals of >100%. The coordination of Cr(III) with picolinic acid may make the metal more genotoxic than other forms of Cr(III). In light of the current results and the known ability of Cr(III) and CrPic to accumulate in tissues, as well as the growing evidence of Cr(III) involvement in Cr(VI)-induced cancers, we caution against ingestion of large doses of CrPic for extended periods.