Skip to main content
Log in

Model reactions of Cr (VI) with DNA mediated by thiol species

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Model reactions were devised to investigate the capacity of physiologically interesting thiol compounds to mediate reactions between CrO4 2− (Cr (VI)) and DNA. The sulfhydryl containing reagents included cysteine, glutathione, apo‐metallothionein (apoMT). Zinc finger 3 of transcription factor IIIA (Zn‐F3) of Xenopus laevis was investigated as a potential redox active site of reaction of Cr (VI) and thiol compounds. The DNA samples were calf thymus DNA and two oligomers, one of them specific for binding Zn-F3. Results showed that in the presence of Cr (VI) apoMT readily participated in damaging DNA in a reaction that appeared to be hydroxyl radical dependent. It also became cross‐linked to oligomer and native DNA samples. In comparison, the other two thiol donors were largely inactive in these assays even though they, like apoMT, were able to reduce Cr (VI) to Cr (III) under the conditions of the experiments. Direct attempts to cross link thiols with DNA in the presence of Cr3+ were unsuccessful at pH 7.4. Together, the results indicate that apoMT can effectively collaborate with Cr (VI) in reactions that are deleterious to DNA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. O'Brien P, Kortenkamp A: Chemical models important in understanding the ways in which chromate can damage DNA. Environ Health Perspect 102: 3–10, 1994

    Google Scholar 

  2. Levina A, Barr-David G, Codd R, Lay PA, Dixon NE, Hammershoi A, Hendry P: In vitro plasmid DNA cleavage by chromium (V) and (IV) 2-hydroxycarboxylato complexes. Chem Res Toxicol 12: 371–381, 1999

    Google Scholar 

  3. Shi X, Ding M, Ye J, Wang S, Leonard SS, Zang L, Castranova V, Vallyathan V, Chiu A, Dalal N, Liu KJ: Cr (IV) causes activation of nuclear transcription factor-kappa B, DNA strand breaks and dG hydroxylation via free radical reactions. Inorg Biochem 75: 37–44, 1999

    Google Scholar 

  4. Myers CR, Myers JM: Iron stimulates the rate of reduction of hexavalent chromium by human microsomes. Carcinogenesis 19: 1029–1038, 1998

    Google Scholar 

  5. Stearns DM, Courtney KD, Giangrande PH, Phieffer LS, Wetterhahn KE: Chromium (VI) reduction by ascorbate: Role of reactive intermediates in DNA damage in vitro. Environ Health Perspect 102: 21–25, 1994

    Google Scholar 

  6. Wiegand HJ, Ottenwalder H, Bolt HM: The reduction of chromium (VI) to chromium (III) by glutathione: an intracellular redox pathway in the metabolism of the carcinogen chromate. Toxicology 33: 341–348, 1984

    Google Scholar 

  7. Sugden KD, Wetterhahn KE: Direct and hydrogen peroxide-induced chromium (V) oxidation of deoxyribose in single-stranded and doublestranded calf thymus DNA. Chem Res Toxicol 10: 1397–1406, 1997

    Google Scholar 

  8. Casadevall M, da Cruz Fresco P, Kortenkamp A: Chromium (VI)-mediated DNA damage: Oxidative pathways resulting in the formation of DNA breaks and abasic sites. Chem Biol Interact 123: 117–132, 1999

    Google Scholar 

  9. Liu S, Medvedovic M, Dixon K: Environ Mutational specificity in a shuttle vector replicating in chromium (VI)-treated mammalian cells. Mol Mutagen 33: 313–319, 1999

    Google Scholar 

  10. Luo H, Lu Y, Mao Y, Shi X, Dalal NS: Role of chromium (IV) in the chromium (VI)-related free radical formation, dG hydroxylation, and DNA damage. J Inorg Biochem 64: 25–35, 1996

    Google Scholar 

  11. Petering D, Fowler B: Roles of metallothionein and related proteins in metal metabolism and toxicity: Problems and perspectives. Environ Health Perspect 65: 217–224, 1986

    Google Scholar 

  12. Krepkiy D, Petering DH: unpublished information

  13. Pattanaik A, Shaw CF III, Petering DH, Garvey J, Kraker AJ: Basal metallothionein in tumors: Widespread presence of apoprotein. J Inorg Biochem 54: 91–105, 1994

    Google Scholar 

  14. Sarkar B: Metal replacement in DNA-binding zinc finger proteins and its relevance to mutagenicity and carcinogenicity through free radical generation. Nutrition 11: 646–649, 1995

    Google Scholar 

  15. Muñoz A, Laib F, Petering DH, Shaw CF III: Characterization of the cadmium complex of peptide 49-61: A putative nucleation center for cadmium-induced folding in rabbit liver metallothionein IIA. J Biol Inorg Chem 4: 495–507, 1999

    Google Scholar 

  16. Sambrook J, Fritsch EF, Maniatis T: In: Molecular Cloning (A Laboratory Manual), 2nd edn. Cold Spring Harbor Laboratory Press, 1989

  17. Zhitkovich A, Voitkun V, Costa M: Glutathione and free amino acids form stable complexes with DNA following exposure of intact mammalian cells to chromate. Carcinogenesis 16: 907–913, 1985

    Google Scholar 

  18. Mao Q, Fulmer P, Li W, DeRose EF, Petering DH: Different conformations and site selectivity of HO2-Co (III)-bleomycin A2 and Co (III)-bleomycin A2 bound to DNA oligomers. J Biol Chem 271: 6185–6191, 1996

    Google Scholar 

  19. Zang WQ, Veldhoen N, Romaniuk PJ: Effects of zinc finger mutations on the nucleic acid binding activities of Xenopus transcription factor IIIA. Biochemistry 34: 15545–15552, 1995

    Google Scholar 

  20. Voitkun V, Zhitkovich A, Costa M: Cr (III)-mediated crosslinks of glutathione or amino acids to the DNA phosphate backbone are mutagenic in human cells. Nucleic Acids Res 26: 2024–2030, 1998

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David H. Petering.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Krepkiy, D., Antholine, W.E., Myers, C. et al. Model reactions of Cr (VI) with DNA mediated by thiol species. Mol Cell Biochem 222, 213–219 (2001). https://doi.org/10.1023/A:1017982717778

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1017982717778

Navigation