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. 1978 Mar;37(3):386–396. doi: 10.1038/bjc.1978.58

Cytotoxic Effects of Hexavalent and Trivalent Chromium on Mammalian Cells In Vitro

A G Levis, V Bianchi, G Tamino, B Pegoraro
PMCID: PMC2009533  PMID: 205233

Abstract

The cytotoxic effects of hexavalent (k2Cr2O7) and trivalent (CrCl3) chromium compounds have been studied in cultured hamster fibroblasts (BHK line) and human epithelial-like cells (HEp line).

K2Cr2O7 stimulates the uptake of labelled thymidine into the soluble intracellular pool (the stimulation of nucleoside uptake represents a specific effect of Cr6+) while Cr3+ always exerts an inhibitory action. DNA Synthesis is inhibited by treatment with both chromium compounds, but especially by K2Cr2O7. Moreover, the effective CrCl3 concentrations reduce the sensitivity of DNA and RNA to hydrolysis with perchloric acid. Treatments with k2Cr2O7 in balanced salt solution, where Cr6+ reduction is less marked, induce more pronounced cytotoxic effects than treatments in complete growth medium.

HEp cells turned out to be more sensitive to K2Cr2O7 than BHK fibroblasts: in the former line TdR uptake is less stimulated, DNA synthesis and cell survival are more affected. Survival of BHK cells to K2Cr2O7 indicates a multi-hit mechanism of cell inactivation, the extrapolation number being about 10.

On the basis of quantitative Cr determinations in the treatment solutions and in the treated cells, the cytotoxic effects of Cr are attributed to the action of Cr6+ at the plasma membrane level on the mechanisms involved in nucleoside uptake, and to the interaction of Cr3+ at the intracellular level with nucleophilic targets on the DNA molecule.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bollum F. J. Mammalian DNA polymerases. Prog Nucleic Acid Res Mol Biol. 1975;15(0):109–144. doi: 10.1016/s0079-6603(08)60118-x. [DOI] [PubMed] [Google Scholar]
  2. Bonatti S., Meini M., Abbondandolo A. Genetic effects of potassium dichromate in Schizosaccharomyces pombe. Mutat Res. 1976 Apr;38(2):147–150. [PubMed] [Google Scholar]
  3. Danchin A. Labelling of biological macromolecules with covalent analogs of Magnesium. II. - Features of the chromic Cr (III) ion. Biochimie. 1975;57(8):875–880. doi: 10.1016/s0300-9084(75)80209-4. [DOI] [PubMed] [Google Scholar]
  4. Fradkin A., Janoff A., Lane B. P., Kuschner M. In vitro transformation of BHK21 cells grown in the presence of calcium chromate. Cancer Res. 1975 Apr;35(4):1058–1063. [PubMed] [Google Scholar]
  5. Furst A., Haro R. T. A survey of metal carcinogenesis. Prog Exp Tumor Res. 1969;12:102–133. [PubMed] [Google Scholar]
  6. GROGAN C. H. Experimental studies in metal cancerigenesis. VIII. On the etiological factor in chromate cancer. Cancer. 1957 May-Jun;10(3):625–638. doi: 10.1002/1097-0142(195705/06)10:3<625::aid-cncr2820100330>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  7. GROGAN C. H. Experimental studies in metal cancerigenesis. XI. On the penetration of chromium into the cell nucleus. Cancer. 1958 Nov-Dec;11(6):1195–1203. doi: 10.1002/1097-0142(195811/12)11:6<1195::aid-cncr2820110615>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  8. HERRMANN H., SPECK L. B. Interaction of chromate with nucleic acids in tissues. Science. 1954 Feb 12;119(3085):221–221. doi: 10.1126/science.119.3085.221. [DOI] [PubMed] [Google Scholar]
  9. HUEPER W. C. Environmental carcinogenesis and cancers. Cancer Res. 1961 Aug;21:842–857. [PubMed] [Google Scholar]
  10. HUEPER W. C. Experimental studies in metal cancerigenesis. X. Cancerigenic effects of chromite ore roast deposited in muscle tissue and pleural cavity of rats. AMA Arch Ind Health. 1958 Oct;18(4):284–291. [PubMed] [Google Scholar]
  11. HUFF J. W., SASTRY K. S., GORDON M. P., WACKER W. E. THE ACTION OF METAL IONS ON TOBACCO MOSAIC VIRUS RIBONUCLEIC ACID. Biochemistry. 1964 Apr;3:501–506. doi: 10.1021/bi00892a006. [DOI] [PubMed] [Google Scholar]
  12. Levis A. G., Buttignol M., Bianchi V., Sponza G. Effects of potassium dichromate on nucleic acid and protein syntheses and on precursor uptake in BHK fibroblasts. Cancer Res. 1978 Jan;38(1):110–116. [PubMed] [Google Scholar]
  13. Levis A. G., Buttignol M. Effects of potassium dichromate on DNA synthesis in hamster fibroblasts. Br J Cancer. 1977 Apr;35(4):496–499. doi: 10.1038/bjc.1977.75. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Levis A. G., Buttignol M., Vettorato L. Inhibition of DNA synthesis in BHK fibroblasts treated in vitro with potassium dichromate. Experientia. 1977 Jan 15;33(1):82–84. doi: 10.1007/BF01936767. [DOI] [PubMed] [Google Scholar]
  15. Maltoni C. Occupational carcinogenesis. Predictive value of carcinogenesis bioassays. Ann N Y Acad Sci. 1976;271:431–443. doi: 10.1111/j.1749-6632.1976.tb23144.x. [DOI] [PubMed] [Google Scholar]
  16. Mertz W. Chromium occurrence and function in biological systems. Physiol Rev. 1969 Apr;49(2):163–239. doi: 10.1152/physrev.1969.49.2.163. [DOI] [PubMed] [Google Scholar]
  17. Nishioka H. Mutagenic activities of metal compounds in bacteria. Mutat Res. 1975 Jun;31(3):185–189. doi: 10.1016/0165-1161(75)90088-6. [DOI] [PubMed] [Google Scholar]
  18. PAYNE W. W. The role of roasted chromite ore in the production of cancer. Arch Environ Health. 1960 Jul;1:20–26. doi: 10.1080/00039896.1960.10662663. [DOI] [PubMed] [Google Scholar]
  19. Petrilli F. L., De Flora S. Toxicity and mutagenicity of hexavalent chromium on Salmonella typhimurium. Appl Environ Microbiol. 1977 Apr;33(4):805–809. doi: 10.1128/aem.33.4.805-809.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Polak L., Turk J. L., Frey J. R. Studies on contact hypersensitivity to chromium compounds. Prog Allergy. 1973;17:145–226. [PubMed] [Google Scholar]
  21. Schoental R. Chromium carcinogenesis, formation of epoxyaldehydes and tanning. Br J Cancer. 1975 Sep;32(3):403–404. doi: 10.1038/bjc.1975.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sirover M. A., Loeb L. A. Infidelity of DNA synthesis in vitro: screening for potential metal mutagens or carcinogens. Science. 1976 Dec 24;194(4272):1434–1436. doi: 10.1126/science.1006310. [DOI] [PubMed] [Google Scholar]
  23. Vallée M. Le système de transport de sulfate chez Chlorella pyrenoidosaa et sa régulation. IV. Etudes avec l'ion chromate. Biochim Biophys Acta. 1969 Apr;173(3):486–500. doi: 10.1016/0005-2736(69)90013-3. [DOI] [PubMed] [Google Scholar]
  24. Venitt S., Levy L. S. Mutagenicity of chromates in bacteria and its relevance to chromate carcinogenesis. Nature. 1974 Aug 9;250(5466):493–495. doi: 10.1038/250493a0. [DOI] [PubMed] [Google Scholar]

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