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

Diane M Stearns, Stacey M. Silveira, Kristina K. Wolf, April M. Luke

Research output: Contribution to journalArticle

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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 μg/cm2 CrPic, which, if fully soluble, would be equivalent to 1mM or 0.44mg/ml CrPic, and would correspond to 1mM Cr(III) or 52μg/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 μg/cm2 CrPic exposure resulted in an average induced mutation frequency (MF) of 58 per 106 surviving cells, or an average 40-fold increase in hprt mutants relative to untreated cells. An equivalent dose of 3 mM Pic was highly cytotoxic and did not yield hprt mutants. The dose range of 0.375-1.5 mM Pic produced a slight increase in hprt mutants, but the increase was not statistically significant. An equivalent dose of 1 mM chromic chloride yielded an induced MF of 9 per 106 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.

Original languageEnglish (US)
Pages (from-to)135-142
Number of pages8
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume513
Issue number1-2
DOIs
StatePublished - Jan 15 2001

Fingerprint

Hypoxanthine Phosphoribosyltransferase
Chromium
Cricetulus
Ovary
CHO Cells
Mutation Rate
Cell Survival
Thioguanine
picolinic acid
United States Food and Drug Administration
Dietary Supplements
Neoplasms
Cell Count
Eating
Metals
Mutation

Keywords

  • Chinese hamster ovary cells
  • Chromium picolinate
  • Hypoxanthine (guanine) phosphoribosyltransferase
  • Mutation frequency

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Genetics

Cite this

Chromium(III) tris(picolinate) is mutagenic at the hypoxanthine (guanine) phosphoribosyltransferase locus in Chinese hamster ovary cells. / Stearns, Diane M; Silveira, Stacey M.; Wolf, Kristina K.; Luke, April M.

In: Mutation Research - Genetic Toxicology and Environmental Mutagenesis, Vol. 513, No. 1-2, 15.01.2001, p. 135-142.

Research output: Contribution to journalArticle

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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 μg/cm2 CrPic, which, if fully soluble, would be equivalent to 1mM or 0.44mg/ml CrPic, and would correspond to 1mM Cr(III) or 52μg/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 μg/cm2 CrPic exposure resulted in an average induced mutation frequency (MF) of 58 per 106 surviving cells, or an average 40-fold increase in hprt mutants relative to untreated cells. An equivalent dose of 3 mM Pic was highly cytotoxic and did not yield hprt mutants. The dose range of 0.375-1.5 mM Pic produced a slight increase in hprt mutants, but the increase was not statistically significant. An equivalent dose of 1 mM chromic chloride yielded an induced MF of 9 per 106 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.",
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AU - Silveira, Stacey M.

AU - Wolf, Kristina K.

AU - Luke, April M.

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N2 - 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 μg/cm2 CrPic, which, if fully soluble, would be equivalent to 1mM or 0.44mg/ml CrPic, and would correspond to 1mM Cr(III) or 52μg/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 μg/cm2 CrPic exposure resulted in an average induced mutation frequency (MF) of 58 per 106 surviving cells, or an average 40-fold increase in hprt mutants relative to untreated cells. An equivalent dose of 3 mM Pic was highly cytotoxic and did not yield hprt mutants. The dose range of 0.375-1.5 mM Pic produced a slight increase in hprt mutants, but the increase was not statistically significant. An equivalent dose of 1 mM chromic chloride yielded an induced MF of 9 per 106 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.

AB - 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 μg/cm2 CrPic, which, if fully soluble, would be equivalent to 1mM or 0.44mg/ml CrPic, and would correspond to 1mM Cr(III) or 52μg/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 μg/cm2 CrPic exposure resulted in an average induced mutation frequency (MF) of 58 per 106 surviving cells, or an average 40-fold increase in hprt mutants relative to untreated cells. An equivalent dose of 3 mM Pic was highly cytotoxic and did not yield hprt mutants. The dose range of 0.375-1.5 mM Pic produced a slight increase in hprt mutants, but the increase was not statistically significant. An equivalent dose of 1 mM chromic chloride yielded an induced MF of 9 per 106 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.

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