title: High-altitude medicines: a short-term genotoxicity study.
abstract: People live in the mountains distributed across the world and are exposed to reduced inspired oxygen and lower barometric pressure along with other factors that lead to high-altitude diseases. The present study was conducted to examine what extent of marketed medicines used in the management of high-altitude sickness has been tested for their genotoxic activity. Comet assay or the single-cell gel electrophoresis was utilized to evaluate genotoxicity of the six medicines on human peripheral whole blood cells and isolated lymphocytes at the concentrations 250 microg/mL, 500 microg/mL and 1 mg/mL. The comet assay endpoints included percentage Tail DNA (% Tail DNA) and olive tail moment (OTM) as they were considered to be sensitive and reliable scores across different laboratories. The results show that dexamethasone, deriphylline and furosemide can induce significant DNA damage in human whole blood and lymphocytes alike. Acetazolamide, ibuprofen and nifedipine show no genotoxic effect, neither on human whole blood nor on human lymphocytes. Taking into account the results of genotoxicity, it will be a prudent choice to restrict the use of these compounds for longer periods, until more information on the in vitro mutagenicity and in vivo genotoxicity studies are available.
authors.affiliation: Centre of Advanced Study, Cell and Chromosome Research, Department of Botany, University of Calcutta, Kolkata, India.
authors.forename: Manosij
authors.initials: M
authors.lastname: Ghosh
authors.forename: Dhrubojyoti
authors.initials: D
authors.lastname: Biswas
authors.forename: Anita
authors.initials: A
authors.lastname: Mukherjee
mesh_terms: D000086:Acetazolamide / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000532:Altitude Sickness / Q000188:drug therapy* / Q000235:genetics; D000704:Analysis of Variance; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020552:Comet Assay; D004247:DNA / Q000187:drug effects / Q000302:isolation & purification; D004249:DNA Damage; D003907:Dexamethasone / Q000009:adverse effects* / Q000627:therapeutic use; D005665:Furosemide / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects / Q000627:therapeutic use; D008214:Lymphocytes / Q000737:chemistry / Q000187:drug effects; D008297:Male; D009152:Mutagenicity Tests / Q000379:methods; D009543:Nifedipine / Q000009:adverse effects / Q000627:therapeutic use; D013806:Theophylline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C021658:deriphyllin; D005665:Furosemide; D003907:Dexamethasone; D004247:DNA; D013806:Theophylline; D009543:Nifedipine; D000086:Acetazolamide; D007052:Ibuprofen