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Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
ISSN: 1596-5996
EISSN: 1596-9827
Vol. 15, No. 12, 2016, pp. 2587-2593
Bioline Code: pr16340
Full paper language: English
Document type: Research Article
Document available free of charge

Tropical Journal of Pharmaceutical Research, Vol. 15, No. 12, 2016, pp. 2587-2593

 en Effect of dose and dosing rate on the mutagenesis of nitric oxide in supF shuttle vector
Kim, Ji Hye & Kim, Min Young


Purpose: To determine how the dose and rate of NO treatment affects mutagenic responses.
Methods: Shuttle vector pSP189 was used to determine the genotoxicity resulting from in vitro exposure to NO using three delivery methods (reactor and Transwell co-culture systems, and NO donor sodium nitroprusside), followed by plasmid replication in bacteria MBL50 and human AD293 cells.
Results: When exposed to preformed 100% NO for 3 h or 1% NO for 35 h using a reactor system, a cumulative dose of 1260 μM × min reduced AD293 cell viability by 46 and 18% and increased mutation frequencies (MFs) 1.9- and 5.3-fold higher than argon control, respectively. Roughly 5-fold increase in MF of the supF gene of AD293 cells co-cultivated with macrophages stimulated with IFN-γ/LPS was also observed. When AD293 cells were treated by SNP, DNA strand breaks were induced and MFs were increased in a dose-dependent manner.
Conclusion: These results provide important clues to how dose and dosing rate of introducing NO may contribute to potential genotoxicity resulting from NO formation in vivo.

AD293 cells; Delivery method; Genotoxicity; Nitric oxide; supF Gene of pSP189 shuttle vector

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