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Genotoxicity of tri- and hexavalent chromium compounds in vivo and their modes of action on DNA damage in vitro.

Fang Z, Zhao M, Zhen H, Chen L, Shi P, Huang Z - PLoS ONE (2014)

Bottom Line: Hexavalent chromium [Cr(VI)] compounds are extensively used in diverse industries, and trivalent chromium [Cr(III)] salts are used as micronutrients and dietary supplements.Cr(VI) intercalates DNA and Cr(III) interferes base pair stacking.Based on our results, we conclude that Cr(III) can directly cause genotoxicity in vivo.

View Article: PubMed Central - PubMed

Affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, China.

ABSTRACT
Chromium occurs mostly in tri- and hexavalent states in the environment. Hexavalent chromium [Cr(VI)] compounds are extensively used in diverse industries, and trivalent chromium [Cr(III)] salts are used as micronutrients and dietary supplements. In the present work, we report that they both induce genetic mutations in yeast cells. They both also cause DNA damage in both yeast and Jurkat cells and the effect of Cr(III) is greater than that of Cr(VI). We further show that Cr(III) and Cr(VI) cause DNA damage through different mechanisms. Cr(VI) intercalates DNA and Cr(III) interferes base pair stacking. Based on our results, we conclude that Cr(III) can directly cause genotoxicity in vivo.

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Related in: MedlinePlus

Both Cr(VI) and Cr(III) induce mutations in yeast.Cells of the yeast strain SJR576 carrying the SUP4-o plasmid were treated with or without CrO3 or CrCl3 for 24 hours and plated on indicator plates to select for sup4-o mutants. Mutational rates were calculated and plotted. The results are the means of three independent experiments. The error bars represent the means ± SD.
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pone-0103194-g001: Both Cr(VI) and Cr(III) induce mutations in yeast.Cells of the yeast strain SJR576 carrying the SUP4-o plasmid were treated with or without CrO3 or CrCl3 for 24 hours and plated on indicator plates to select for sup4-o mutants. Mutational rates were calculated and plotted. The results are the means of three independent experiments. The error bars represent the means ± SD.

Mentions: To evaluate the potential effects of Cr(III) and Cr(VI) in causing mutations, we assayed the well-defined SUP4-o allele. This allele encode a mutant tRNA that suppresses ochre stop codons by inserting a tyrosine. Two ochre alleles, ade2-1oc and can1-100oc, were used to monitor the loss of SUP4-o function. The ade2-1oc mutation causes adenine auxotrophy as manifested as red colony color. The can1-100oc mutation causes resistance to cananvanine. The presence of a functional SUP4-o allele renders cells containing the ade2-1oc and can1-100oc form white colonies that are sensitive to canavanine. Mutations that inactivate SUP4-o can be identified by the simultaneous loss of suppression of both ade2-1 and can1-100 alleles, resulting in red and canavanine resistant colonies. Using this system, we tested whether Cr(VI) and Cr(III) might increase mutational frequency in yeast. In untreated cells, the frequency of loss of SUP4-o function was about 6.32×10−6. In CrO3 (at 300 µM) and CrCl3 (at 150 µM) treated cells, the frequency was increased to 31.6×10−6 and 33.86×10−6, respectively (Fig. 1). Therefore, Cr(VI) and Cr(III) significantly induce the loss of SUP4-o function in yeast cells (P<0.001) (Fig. 1).


Genotoxicity of tri- and hexavalent chromium compounds in vivo and their modes of action on DNA damage in vitro.

Fang Z, Zhao M, Zhen H, Chen L, Shi P, Huang Z - PLoS ONE (2014)

Both Cr(VI) and Cr(III) induce mutations in yeast.Cells of the yeast strain SJR576 carrying the SUP4-o plasmid were treated with or without CrO3 or CrCl3 for 24 hours and plated on indicator plates to select for sup4-o mutants. Mutational rates were calculated and plotted. The results are the means of three independent experiments. The error bars represent the means ± SD.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128586&req=5

pone-0103194-g001: Both Cr(VI) and Cr(III) induce mutations in yeast.Cells of the yeast strain SJR576 carrying the SUP4-o plasmid were treated with or without CrO3 or CrCl3 for 24 hours and plated on indicator plates to select for sup4-o mutants. Mutational rates were calculated and plotted. The results are the means of three independent experiments. The error bars represent the means ± SD.
Mentions: To evaluate the potential effects of Cr(III) and Cr(VI) in causing mutations, we assayed the well-defined SUP4-o allele. This allele encode a mutant tRNA that suppresses ochre stop codons by inserting a tyrosine. Two ochre alleles, ade2-1oc and can1-100oc, were used to monitor the loss of SUP4-o function. The ade2-1oc mutation causes adenine auxotrophy as manifested as red colony color. The can1-100oc mutation causes resistance to cananvanine. The presence of a functional SUP4-o allele renders cells containing the ade2-1oc and can1-100oc form white colonies that are sensitive to canavanine. Mutations that inactivate SUP4-o can be identified by the simultaneous loss of suppression of both ade2-1 and can1-100 alleles, resulting in red and canavanine resistant colonies. Using this system, we tested whether Cr(VI) and Cr(III) might increase mutational frequency in yeast. In untreated cells, the frequency of loss of SUP4-o function was about 6.32×10−6. In CrO3 (at 300 µM) and CrCl3 (at 150 µM) treated cells, the frequency was increased to 31.6×10−6 and 33.86×10−6, respectively (Fig. 1). Therefore, Cr(VI) and Cr(III) significantly induce the loss of SUP4-o function in yeast cells (P<0.001) (Fig. 1).

Bottom Line: Hexavalent chromium [Cr(VI)] compounds are extensively used in diverse industries, and trivalent chromium [Cr(III)] salts are used as micronutrients and dietary supplements.Cr(VI) intercalates DNA and Cr(III) interferes base pair stacking.Based on our results, we conclude that Cr(III) can directly cause genotoxicity in vivo.

View Article: PubMed Central - PubMed

Affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, China.

ABSTRACT
Chromium occurs mostly in tri- and hexavalent states in the environment. Hexavalent chromium [Cr(VI)] compounds are extensively used in diverse industries, and trivalent chromium [Cr(III)] salts are used as micronutrients and dietary supplements. In the present work, we report that they both induce genetic mutations in yeast cells. They both also cause DNA damage in both yeast and Jurkat cells and the effect of Cr(III) is greater than that of Cr(VI). We further show that Cr(III) and Cr(VI) cause DNA damage through different mechanisms. Cr(VI) intercalates DNA and Cr(III) interferes base pair stacking. Based on our results, we conclude that Cr(III) can directly cause genotoxicity in vivo.

Show MeSH
Related in: MedlinePlus