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

Toxins

Steven A. Akman¹  Marissa Adams¹  Doug Case²  Gyungse Park³ 

[1] Department of Cancer Biology, Wake Forest University Health Sciences, Winston-Salem, North Carolina, NC, USA;Department of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina, NC, USA;Department of Chemistry, College of Science and Technology, Kunsan National University, Miryong-Dong, Kusan, Korea;

关键词: ochratoxin A;    mutagenicity;    DNA adduct;    genotoxicity;    carcinogenesis;   

DOI  :  10.3390/toxins4040267

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.