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Toxins 2012, 4(4), 267-280; doi:10.3390/toxins4040267
Article

Mutagenicity of Ochratoxin A and Its Hydroquinone Metabolite in the SupF Gene of the Mutation Reporter Plasmid Ps189

1,* , 1
, 2
, 3
 and 4,*
Received: 9 February 2012; in revised form: 29 March 2012 / Accepted: 6 April 2012 / Published: 16 April 2012
(This article belongs to the Special Issue Ochratoxins 2011-2012)
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Abstract: Ochratoxin A (OTA) is a mycotoxin that enhances renal tumor formation in the outer medulla of male rat kidney. Direct DNA damage and subsequent mutagenicity may contribute to these processes. In this study we have determined whether OTA in the absence or presence of activated rat liver microsomes (RLM) or redox-active transition metals (Fe(III) or Cu(II)) causes promutagenic DNA damage in the supF gene of the mutation reporter plasmid pS189 replicating in human Ad293 cells. In addition, we have assessed the mutagenicity of the hydroquinone metabolite (OTHQ) of OTA in the absence or presence of cysteine without added cofactors. Our results show that oxidation of OTA, either by RLM or by transition metal ions, activates OTA to a directly genotoxic mutagen(s). The Fe(III)/OTA system was the most potent mutagen in our experimental system, causing a 32-fold increase in mutant fraction (MF) above the spontaneous control MF. The Cu(II)/OTA system caused a 9-fold increase in MF, while a 6–10-fold increase in MF was observed for OTA in the presence of RLM. The OTHQ metabolite is also mutagenic, especially in the presence of cysteine, in which a 6-fold increase in MF was observed. Our data provide further insight into OTA bioactivation that may account for its in vivo mutagenicity in male rat kidney.
Keywords: ochratoxin A; mutagenicity; DNA adduct; genotoxicity; carcinogenesis ochratoxin A; mutagenicity; DNA adduct; genotoxicity; carcinogenesis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Akman, S.A.; Adams, M.; Case, D.; Park, G.; Manderville, R.A. Mutagenicity of Ochratoxin A and Its Hydroquinone Metabolite in the SupF Gene of the Mutation Reporter Plasmid Ps189. Toxins 2012, 4, 267-280.

AMA Style

Akman SA, Adams M, Case D, Park G, Manderville RA. Mutagenicity of Ochratoxin A and Its Hydroquinone Metabolite in the SupF Gene of the Mutation Reporter Plasmid Ps189. Toxins. 2012; 4(4):267-280.

Chicago/Turabian Style

Akman, Steven A.; Adams, Marissa; Case, Doug; Park, Gyungse; Manderville, Richard A. 2012. "Mutagenicity of Ochratoxin A and Its Hydroquinone Metabolite in the SupF Gene of the Mutation Reporter Plasmid Ps189." Toxins 4, no. 4: 267-280.


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