Mutant frequency in comparison to oxidative DNA damage induced by ochratoxin A in L5178Y tk+/− (3.7.2C) mouse lymphoma cells. (April 2014)

• Record Type: Journal Article
• Authors: Ali, Rahat; Guo, Xiaoqing; Lin, Haixia; Khan, Qaiser M.; Ismail, Muhammad; Waheed, Usman; Ali, Tayyaba; Bhalli, Javed A.
• Is Part Of: Drug and chemical toxicology. Volume 37:Number 2(2014:Apr.)
• Page Start: 227
• Page End: 232
• Publication Date: 2014-04
• Subjects: Toxicology -- Periodicals; Drugs -- Toxicology -- Periodicals; Toxicology, Experimental -- Periodicals; 615.9005
• DOI: 10.3109/01480545.2013.838775
• Languages: English
• ISSNs: 0148-0545

Abstract

<abstract> <title>Abstract</title> <p>Ochratoxin A (OTA) is a naturally occurring mycotoxin that contaminates animal feed and human food. OTA is nephrotoxic, hepatotoxic, immunosuppressive and a potent renal carcinogen in rodents. In the present study, we evaluated the genotoxicity of OTA in L5178Y <italic>tk</italic>^+/− (3.7.2C) mouse lymphoma cells using the microwell version of the mouse lymphoma gene mutation assay (MLA) and the comet assay modified to detect oxidative DNA damage. Cells were treated for 4 hours with 0, 5, 10, 25, 50 or 100 µM of OTA in the presence and absence of exogenous metabolic activation (S9). Benzo[<italic>a</italic>]pyrene (1 µg/mL) and 4-nitroquinoline-1-oxide (0.1 µg/mL) were used as positive control with and without S9, respectively. OTA treatment produced dose-dependent increases in cytotoxicity and <italic>tk</italic> mutant frequency, with significant increases in mutant frequency detected at concentrations ≥25 µM with and without S9. Similarly treated cells were used for the comet assay conducted with and without formamidopyrimidine-DNA glycosylase for the determination of oxidative DNA damage. OTA exposure resulted in a significant increase in both direct and oxidative DNA damage, with induction of oxidative damage being greater. The results indicate that OTA is mutagenic in mouse lymphoma assay; and that OTA-generated oxidative DNA damage is, at least partially, responsible for its mutagenicity in the assay.</p> </abstract>