Nucleic Acids Research, Vol 26, Issue 8 2024-2030, Copyright © 1998 by Oxford University Press
V Voitkun, A Zhitkovich and M Costa
Carcinogenic Cr(VI) compounds were previously found to induce amino
acid/glutathione-Cr(III)-DNA crosslinks with the site of adduction on the
phosphate backbone. Utilizing the pSP189 shuttle vector plasmid we found
that these ternary DNA adducts were mutagenic in human fibroblasts. The
Cr(III)-glutathione adduct was the most potent in this assay, followed by
Cr(III)-His and Cr(III)-Cys adducts. Binary Cr(III)- DNA complexes were
only weakly mutagenic, inducing a significant response only at a 10 times
higher number of adducts compared with Cr(III)-glutathione. Single base
substitutions at the G:C base pairs were the predominant type of mutations
for all Cr(III) adducts. Cr(III), Cr(III)-Cys and Cr(III)-His adducts
induced G:C-->A:T transitions and G:C-->T:A transversions with almost
equal frequency, whereas the Cr(III)-glutathione mutational spectrum was
dominated by G:C-->T:A transversions. Adduct-induced mutations were
targeted toward G:C base pairs with either A or G in the 3' position to the
mutated G, while spontaneous mutations occurred mostly at G:C base pairs
with a 3' A. No correlation was found between the sites of DNA adduction
and positions of base substitution, as adducts were formed randomly on DNA
with no base specificity. The observed mutagenicity of Cr(III)-induced
phosphotriesters demonstrates the importance of a Cr(III)-dependent pathway
in Cr(VI) carcinogenicity.
ARTICLES
Cr(III)-mediated crosslinks of glutathione or amino acids to the DNA phosphate backbone are mutagenic in human cells
Department of Environmental Medicine and The Kaplan Comprehensive Cancer Center, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. Brooks, T. J. O'Brien, S. Ceryak, J. P. Wise Sr, S. S. Wise, J. P. Wise Jr, E. DeFabo, and S. R. Patierno Excision repair is required for genotoxin-induced mutagenesis in mammalian cells Carcinogenesis, May 1, 2008; 29(5): 1064 - 1069. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Soliman, A.-C. Lo, M. Banerjee, N. El-Ghawalby, H. M. Khaled, S. Bayoumi, I. A. Seifeldin, A. Abdel-Aziz, J. L. Abbruzzese, J. K. Greenson, et al. Differences in K-ras and p53 gene mutations among pancreatic adenocarcinomas associated with regional environmental pollution Carcinogenesis, August 1, 2007; 28(8): 1794 - 1799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. F. Ackerley, Y. Barak, S. V. Lynch, J. Curtin, and A. Matin Effect of Chromate Stress on Escherichia coli K-12 J. Bacteriol., May 1, 2006; 188(9): 3371 - 3381. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Kirpnick-Sobol, R. Reliene, and R. H. Schiestl Carcinogenic Cr(VI) and the Nutritional Supplement Cr(III) Induce DNA Deletions in Yeast and Mice. Cancer Res., April 1, 2006; 66(7): 3480 - 3484. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Priester, S. G. Olson, S. M. Webb, M. P. Neu, L. E. Hersman, and P. A. Holden Enhanced Exopolymer Production and Chromium Stabilization in Pseudomonas putida Unsaturated Biofilms. Appl. Envir. Microbiol., March 1, 2006; 72(3): 1988 - 1996. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Arakawa, F. Wu, M. Costa, W. Rom, and M.-s. Tang Sequence specificity of Cr(III)-DNA adduct formation in the p53 gene: NGG sequences are preferential adduct-forming sites Carcinogenesis, March 1, 2006; 27(3): 639 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Russo, A. Catassi, A. Cesario, A. Imperatori, N. Rotolo, M. Fini, P. Granone, and L. Dominioni Molecular Mechanisms of Hexavalent Chromium-Induced Apoptosis in Human Bronchoalveolar Cells Am. J. Respir. Cell Mol. Biol., December 1, 2005; 33(6): 589 - 600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Peterson-Roth, M. Reynolds, G. Quievryn, and A. Zhitkovich Mismatch Repair Proteins Are Activators of Toxic Responses to Chromium-DNA Damage Mol. Cell. Biol., May 1, 2005; 25(9): 3596 - 3607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Reynolds, E. Peterson, G. Quievryn, and A. Zhitkovich Human Nucleotide Excision Repair Efficiently Removes Chromium-DNA Phosphate Adducts and Protects Cells against Chromate Toxicity J. Biol. Chem., July 16, 2004; 279(29): 30419 - 30424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Feng, W. Hu, W. N. Rom, M. Costa, and M.-S. Tang Chromium(VI) exposure enhances polycyclic aromatic hydrocarbon-DNA binding at the p53 gene in human lung cells Carcinogenesis, April 1, 2003; 24(4): 771 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.G. Medeiros, A.S. Rodrigues, M.C. Batoreu, A. Laires, J. Rueff, and A. Zhitkovich Elevated levels of DNA-protein crosslinks and micronuclei in peripheral lymphocytes of tannery workers exposed to trivalent chromium Mutagenesis, January 1, 2003; 18(1): 19 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A D Dayan and A J Paine Mechanisms of chromium toxicity, carcinogenicity and allergenicity: Review of the literature from 1985 to 2000 Human and Experimental Toxicology, September 1, 2001; 20(9): 439 - 451. [Abstract] [PDF]
|
|