title: Mutant frequency in comparison to oxidative DNA damage induced by ochratoxin A in L5178Y tk+/- (3.7.2C) mouse lymphoma cells.
abstract: 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 tk(+/-) (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[a]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 tk 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.
authors.affiliation: National Center for Toxicological Research, U.S. Food and Drug Administration , Jefferson, Arkansas , USA .
authors.forename: Rahat
authors.initials: R
authors.lastname: Ali
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Guo
authors.forename: Haixia
authors.initials: H
authors.lastname: Lin
authors.forename: Qaiser M
authors.initials: QM
authors.lastname: Khan
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ismail
authors.forename: Usman
authors.initials: U
authors.lastname: Waheed
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Ali
authors.forename: Javed A
authors.initials: JA
authors.lastname: Bhalli
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D045744:Cell Line, Tumor; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008223:Lymphoma / Q000473:pathology*; D051379:Mice; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects; D009793:Ochratoxins / Q000008:administration & dosage / Q000633:toxicity*; D010084:Oxidation-Reduction
chemical_list: D009153:Mutagens; D009793:Ochratoxins; C025589:ochratoxin A; D001564:Benzo(a)pyrene; D015112:4-Nitroquinoline-1-oxide