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Chemical Compound Review

Chromium(VI)     chromium(+6) cation

Synonyms: Chromium(6+), NCI-C04273, CR+6, Cr6+, CHEBI:33007, ...
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Disease relevance of Cr(VI)

  • Selection for Cr(VI) resistant, MMR-deficient cells may explain the very high frequency of lung cancers with microsatellite instability among chromate workers [1].
  • The lung and kidney may be more sensitive than liver to chromium-induced DNA damage, an observation which correlates with the reported toxicity and carcinogenicity data for chromium(VI) in both animals and humans [2].
  • Chromium in the form of Cr(III) as well as Cr(VI) diminished the fidelity by which Escherichia coli DNA polymerase I copies polynucleotide templates [3].
  • Incubation of rat liver cytosolic or microsomal fractions with chromium(VI) led to a dramatic decrease in chromium(VI) mutagenicity, as determined by the Ames Salmonella assay using the TA100 tester strain [4].
  • These results confirm the view that the active mutagenic agent in intact cell systems is Cr(VI), but indicate that industrial Cr(III) compounds cannot be considered genetically inert, as they can be contaminated by Cr(VI) and induce chromosomal aberrations [5].

Psychiatry related information on Cr(VI)


High impact information on Cr(VI)


Chemical compound and disease context of Cr(VI)


Biological context of Cr(VI)


Anatomical context of Cr(VI)

  • Of three enzyme inducers injected i.p. which modified the spectral properties and/or concentration of cytochromes P-450 in liver and lung microsomes, only Aroclor 1254 proved to stimulate chromium(VI) metabolism in lung cells [22].
  • In the lung cytosol, a slight yet significant stimulation of some of these enzyme activities was determined by the daily intratracheal instillations of high doses of chromium(VI) itself for 4 weeks, a condition which has been found to enhance the pulmonary metabolism of this metal ion [23].
  • Specificity and inducibility of the metabolic reduction of chromium(VI) mutagenicity by subcellular fractions of rat tissues [22].
  • Chromium(VI) salts are well known to be mutagens and carcinogens and to easily cross the cell membranes [24].
  • NER deficiency created by the loss of XPA in fibroblasts or by knockdown of this protein by stable expression of small interfering RNA in H460 cells increased apoptosis and clonogenic death by Cr(VI), providing genetic evidence for the role of monofunctional chromium-DNA adducts in the toxic effects of this metal [25].

Associations of Cr(VI) with other chemical compounds


Gene context of Cr(VI)

  • p38 Signaling-mediated hypoxia-inducible factor 1alpha and vascular endothelial growth factor induction by Cr(VI) in DU145 human prostate carcinoma cells [28].
  • Chromium (VI) activates ataxia telangiectasia mutated (ATM) protein. Requirement of ATM for both apoptosis and recovery from terminal growth arrest [29].
  • Oppositely, activation of ERK, JNK and p38 by Cr(VI) does not affect cytotoxicity [30].
  • The activated p38 decreased markedly and rapidly and the activated JNK decreased gradually when Cr(VI) was removed from media [30].
  • These results, taken together with the recombinogenic effects of Cr(VI) in yeast containing a functional RAD52 gene, suggest that RAD52-mediated recombination is critical for the normal processing of lethal Cr-induced genetic lesions and exit from G(2) arrest [31].

Analytical, diagnostic and therapeutic context of Cr(VI)


  1. Mismatch repair proteins are activators of toxic responses to chromium-DNA damage. Peterson-Roth, E., Reynolds, M., Quievryn, G., Zhitkovich, A. Mol. Cell. Biol. (2005) [Pubmed]
  2. Chromium(VI)-induced DNA lesions and chromium distribution in rat kidney, liver, and lung. Tsapakos, M.J., Hampton, T.H., Wetterhahn, K.E. Cancer Res. (1983) [Pubmed]
  3. Effects of arsenic, selenium, and chromium on the fidelity of DNA synthesis. Tkeshelashvili, L.K., Shearman, C.W., Zakour, R.A., Koplitz, R.M., Loeb, L.A. Cancer Res. (1980) [Pubmed]
  4. Reduction of chromium(VI) to chromium(V) by rat liver cytosolic and microsomal fractions: is DT-diaphorase involved? Aiyar, J., De Flora, S., Wetterhahn, K.E. Carcinogenesis (1992) [Pubmed]
  5. Cytotoxic, mutagenic and clastogenic effects of industrial chromium compounds. Venier, P., Montaldi, A., Majone, F., Bianchi, V., Levis, A.G. Carcinogenesis (1982) [Pubmed]
  6. Threshold mechanisms and site specificity in chromium(VI) carcinogenesis. De Flora, S. Carcinogenesis (2000) [Pubmed]
  7. Effect of coupled dissolution and redox reactions on Cr(VI)aq attenuation during transport in the sediments under hyperalkaline conditions. Qafoku, N.P., Ainsworth, C.C., Szecsody, J.E., Qafoku, O.S., Heald, S.M. Environ. Sci. Technol. (2003) [Pubmed]
  8. Hexavalent chromium effects on motor activity and some metabolic aspects of Wistar albino rats. Diaz-Mayans, J., Laborda, R., Nuñez, A. Comp. Biochem. Physiol. C, Comp. Pharmacol. Toxicol. (1986) [Pubmed]
  9. Modification of chromium(VI)-induced DNA damage by glutathione and cytochromes P-450 in chicken embryo hepatocytes. Cupo, D.Y., Wetterhahn, K.E. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  10. Metal ion-dependent hydrogen peroxide-induced DNA damage is more sequence specific than metal specific. Rodriguez, H., Holmquist, G.P., D'Agostino, R., Keller, J., Akman, S.A. Cancer Res. (1997) [Pubmed]
  11. Role of valence state and solubility of chromium compounds on induction of cytotoxicity, mutagenesis, and anchorage independence in diploid human fibroblasts. Biedermann, K.A., Landolph, J.R. Cancer Res. (1990) [Pubmed]
  12. Role of p53 tumor suppressor gene in the toxicity of TCDD, endrin, naphthalene, and chromium (VI) in liver and brain tissues of mice. Bagchi, D., Balmoori, J., Bagchi, M., Ye, X., Williams, C.B., Stohs, S.J. Free Radic. Biol. Med. (2000) [Pubmed]
  13. NADPH-dependent flavoenzymes catalyze one electron reduction of metal ions and molecular oxygen and generate hydroxyl radicals. Shi, X.L., Dalal, N.S. FEBS Lett. (1990) [Pubmed]
  14. Simultaneous chromium reduction and phenol degradation in a coculture of Escherichia coli ATCC 33456 and Pseudomonas putida DMP-1. Shen, H., Wang, Y.T. Appl. Environ. Microbiol. (1995) [Pubmed]
  15. NAD(P)H-dependent chromium (VI) reductase of Pseudomonas ambigua G-1: a Cr(V) intermediate is formed during the reduction of Cr(VI) to Cr(III). Suzuki, T., Miyata, N., Horitsu, H., Kawai, K., Takamizawa, K., Tai, Y., Okazaki, M. J. Bacteriol. (1992) [Pubmed]
  16. Cr(VI) reduction by sulfidogenic and nonsulfidogenic microbial consortia. Arias, Y.M., Tebo, B.M. Appl. Environ. Microbiol. (2003) [Pubmed]
  17. Role of reactive oxygen species and p53 in chromium(VI)-induced apoptosis. Ye, J., Wang, S., Leonard, S.S., Sun, Y., Butterworth, L., Antonini, J., Ding, M., Rojanasakul, Y., Vallyathan, V., Castranova, V., Shi, X. J. Biol. Chem. (1999) [Pubmed]
  18. Protective roles of NF-kappa B for chromium(VI)-induced cytotoxicity is revealed by expression of Ikappa B kinase-beta mutant. Chen, F., Bower, J., Leonard, S.S., Ding, M., Lu, Y., Rojanasakul, Y., Kung, H.F., Vallyathan, V., Castranova, V., Shi, X. J. Biol. Chem. (2002) [Pubmed]
  19. Chromium(VI) inhibits the transcriptional activity of nuclear factor-kappaB by decreasing the interaction of p65 with cAMP-responsive element-binding protein-binding protein. Shumilla, J.A., Broderick, R.J., Wang, Y., Barchowsky, A. J. Biol. Chem. (1999) [Pubmed]
  20. Chromium(VI) down-regulates heavy metal-induced metallothionein gene transcription by modifying transactivation potential of the key transcription factor, metal-responsive transcription factor 1. Majumder, S., Ghoshal, K., Summers, D., Bai, S., Datta, J., Jacob, S.T. J. Biol. Chem. (2003) [Pubmed]
  21. Sialoglycoprotein and carbohydrate complexes in chromium toxicity. Codd, R., Irwin, J.A., Lay, P.A. Current opinion in chemical biology. (2003) [Pubmed]
  22. Specificity and inducibility of the metabolic reduction of chromium(VI) mutagenicity by subcellular fractions of rat tissues. Petrilli, F.L., Camoirano, A., Bennicelli, C., Zanacchi, P., Astengo, M., De Flora, S. Cancer Res. (1985) [Pubmed]
  23. Prominent role of DT-diaphorase as a cellular mechanism reducing chromium(VI) and reverting its mutagenicity. De Flora, S., Morelli, A., Basso, C., Romano, M., Serra, D., De Flora, A. Cancer Res. (1985) [Pubmed]
  24. A comparative study of calf thymus DNA binding to Cr(III) and Cr(VI) ions. Evidence for the guanine N-7-chromium-phosphate chelate formation. Arakawa, H., Ahmad, R., Naoui, M., Tajmir-Riahi, H.A. J. Biol. Chem. (2000) [Pubmed]
  25. Human nucleotide excision repair efficiently removes chromium-DNA phosphate adducts and protects cells against chromate toxicity. Reynolds, M., Peterson, E., Quievryn, G., Zhitkovich, A. J. Biol. Chem. (2004) [Pubmed]
  26. Binding of chromium to chromatin and DNA from liver and kidney of rats treated with sodium dichromate and chromium(III) chloride in vivo. Cupo, D.Y., Wetterhahn, K.E. Cancer Res. (1985) [Pubmed]
  27. S-Nitrosylation of Bcl-2 Inhibits Its Ubiquitin-Proteasomal Degradation: A NOVEL ANTIAPOPTOTIC MECHANISM THAT SUPPRESSES APOPTOSIS. Azad, N., Vallyathan, V., Wang, L., Tantishaiyakul, V., Stehlik, C., Leonard, S.S., Rojanasakul, Y. J. Biol. Chem. (2006) [Pubmed]
  28. p38 Signaling-mediated hypoxia-inducible factor 1alpha and vascular endothelial growth factor induction by Cr(VI) in DU145 human prostate carcinoma cells. Gao, N., Jiang, B.H., Leonard, S.S., Corum, L., Zhang, Z., Roberts, J.R., Antonini, J., Zheng, J.Z., Flynn, D.C., Castranova, V., Shi, X. J. Biol. Chem. (2002) [Pubmed]
  29. Chromium (VI) activates ataxia telangiectasia mutated (ATM) protein. Requirement of ATM for both apoptosis and recovery from terminal growth arrest. Ha, L., Ceryak, S., Patierno, S.R. J. Biol. Chem. (2003) [Pubmed]
  30. Comparison of roles of three mitogen-activated protein kinases induced by chromium(VI) and cadmium in non-small-cell lung carcinoma cells. Chuang, S.M., Yang, J.L. Mol. Cell. Biochem. (2001) [Pubmed]
  31. Effects of hexavalent chromium on the survival and cell cycle distribution of DNA repair-deficient S. cerevisiae. O'Brien, T.J., Fornsaglio, J.L., Ceryak, S., Patierno, S.R. DNA Repair (Amst.) (2002) [Pubmed]
  32. Role of solubilized chromium in the induction of morphological transformation of Syrian hamster embryo (SHE) cells by particulate chromium(VI) compounds. Elias, Z., Poirot, O., Baruthio, F., Danière, M.C. Carcinogenesis (1991) [Pubmed]
  33. Selective preconcentration and determination of chromium(VI) using a flat sheet polymer inclusion sorbent: potential application for Cr(VI) determination in real samples. Scindia, Y.M., Pandey, A.K., Reddy, A.V., Manohar, S.B. Anal. Chem. (2002) [Pubmed]
  34. Speciation of chromium (III) and chromium (VI) by capillary electrophoresis with contactless conductometric detection and dual opposite end injection. Kubán, P., Kubán, P., Kubán, V. Electrophoresis (2003) [Pubmed]
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