Mutagenicity of a series of hexacoordinate chromium(III) compounds

Warren, Guylyn; Schultz, Paul N.; Bancroft, Dan; Bennett, Kim D.; Abbott, E. H.; Rogers, Samuel J.

doi:10.1016/0165-1218(81)90073-2

Cited by 75 publications

(30 citation statements)

References 18 publications

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“…Nevertheless, Criii compounds can reach the nucleus of cells within target organs (10) and, once inside the cell, Crii" species can be mutagenic (11)(12)(13) and genotoxic (13). Recent evidence suggests that CrIII species, although previously considered "kinetically inert," can readily bind to nucleic acids in vitro and can even act as redox agents when complexed to a conjugated aromatic ligand (11,14). Crl" is also reported to induce a small (2-fold) increase in misincorporation by DNA polymerases during DNA replication in vitro (15,16).…”

Section: Introductionmentioning

confidence: 99%

A Possible Role for Chromium(III) in Genotoxicity

Snow¹

1991

Environmental Health Perspectives

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Chromium is found in the environment in two major forms: reduced Cil' and CrVy, or chromate.Chromate, the most biologically active species, is readily taken up by living cells and reduced intracellularly, via reactive intermediates, to stable Cr"I species. Cr'l, the most abundant form of chromium in the environment, does not readily cross cell membranes and is relatively inactive in vivo. However, intracellular Crl" can react slowly with both nucleic acids and proteins and can be genotoxic. We have investigated the genotoxicity of Cr"P in vitro using a DNA replication assay and in vivo by CaCl2-mediated transfection of chromium-treated DNA into Escherichia coli. When DNA replication was measured on a Cr"'-treated template using purified DNA polymerases (either bacterial or mammalian), both the rate of DNA replication and the amount of incorporation per polymerase binding event (processivity) were greatly increased relative to controls. When transfected into E. coli, Cr"l-treated M13mp2 bacteriophage DNA showed a dose-dependent increase in mutation frequency. These results suggest that Cr"' alters the interaction between the DNA template and the polymerase such that the binding strength of the DNA polymerase is increased and the fidelity of DNA replication is decreased. These interactions may contribute to the mutagenicity of chromium ions in vivo and suggest that Cr"' can contribute to chromiummediated carcinogenesis.

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Section: Introductionmentioning

confidence: 99%

A Possible Role for Chromium(III) in Genotoxicity

Snow¹

1991

Environmental Health Perspectives

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“…The organic part of the complex probably made some of them able to penetrate bacterial cells and the mutagenic activity could be revealed, as was discussed, for example, in the case of Cr(III)-organic complexes (Warren et al 1981, Szyba et al 1992, Gulanowski et al 1994). In the case of our complexes, the role of the C1 anion seems to be crucial, since only CI -containing complexes were found to be mutagenic.…”

Section: Discussionmentioning

confidence: 99%

Mutagenic activity of group VIII metal-organic complexes in the Ames test: evaluation of potential glucose biosensor components

et al. 1995

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Five novel tris-(4,4'-substituted-2,2'-bipyridine) complexes of the group VIII metals [Fe(ll), Ru(ll) and Os(ll)](all having been previously examined electrochemically with respect to their ability to act as electron-transfer mediators for redox enzymes) were assayed in the Ames test to evaluate their mutagenic activity. For the bipyridine complexes, some complexes did exhibit mutagenic activity in the circumstances of this test, whereas others did not. this is comparable to the results known from the literature for ferrocene mediators. There was no specific correlation with the identities of the metal and ligand type; the possible explanations of the results are discussed in this paper. It seems probable that the penetration of the whole compound inside bacterial cells depends on the organic part of a complex, with only then the possible genotoxic activity of the complex being revealed. In view of our mutagenic test results, such complexes found to be mutagenic should not be taken into consideration as components of implanted glucose sensors in future in vivo experiments.

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“…However, in vitro studies showed that the Cr(III) ions are bound to DNA in the cell-free system (Wolf et al 1989, Snow 1991, Gulanowski et al 1992 inducing DNA crosslinking (Snow & Xu 1989, Gulanowski et al 1992, DNA-protein cross-links (Kortenkamp et al 1992) and DNA condensation (Osterberg et al 1984), and also decreasing the DNA replication fidelity (Snow 1991). In the bacterial tests some Cr(III) complexes were found to be mutagenic (Warren et al 1981, Snow 1991. At the same time the Cr(III) ions appeared to be essential for animals and humans (Morris et al 1988).…”

Section: Introductionmentioning

confidence: 99%

In vitro studies on the DNA impairments induced by Cr(III) complexes with cellular reductants

et al. 1994

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The influence of Cr(III) complexes with ascorbic acid, cysteine and glutathione on DNA has been studied spectrophotometrically and chromatographically. The toxic and genotoxic activities of these complexes were also investigated. It was found that these complexes bind to DNA weaker than hexaaqua Cr(III) complexes. It could be explained through the greater strength of the bi- and tridentate ligands coordinated to chromium in comparison to water molecules. The formation of DNA-DNA intermolecular bonds and DNA interstrand cross-linking has been also observed. These complexes were found to be non-toxic and non-genotoxic in the bacterial test.

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Mutagenicity of a series of hexacoordinate chromium(III) compounds

Cited by 75 publications

References 18 publications

A Possible Role for Chromium(III) in Genotoxicity

A Possible Role for Chromium(III) in Genotoxicity

Mutagenic activity of group VIII metal-organic complexes in the Ames test: evaluation of potential glucose biosensor components

In vitro studies on the DNA impairments induced by Cr(III) complexes with cellular reductants

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