Clastogenic effect of fenfluramine in mice bone marrow cells in vivo

Agarwal, Kalpana ; Mukherjee, Anita ; Sharma, Archana ; Sharma, Ramesh ; Bhardwaj, Kuldip Raj ; Sen, Soumitra (1992) Clastogenic effect of fenfluramine in mice bone marrow cells in vivo Environmental and Molecular Mutagenesis, 19 (4). pp. 323-326. ISSN 0893-6692

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Fenfluramine, an amphetamine derivative used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice using two cytogenetic endpoints for assessing its genotoxic and clastogenic potentials. Concentrations of 0.75, 1.5, 3.0, and 5.0 mg/kg b.w. were administered orally for the study of sister chromatid exchange frequencies and chromosome aberrations (CA). SCE frequencies showed a positive dose response; 1.5 mg/kg being the minimum effective concentration. Fen caused a prolongation of cell cycle at all concentrations. Except for the minimum therapeutic dose (0.75 mg), all other doses (1.5, 3.0, and 5.0 mg) showed a significant increase in the percentage of damaged cells over that of the vehicle control. The degree of clastogenicity was directly proportional to the dosage used and inversely related with the duration of treatment. A gradual reduction of the clastogenic potential was observed after 12 and 24 hr of exposure, indicating that the maximum effect occurs at the middle or late synthetic phase of the cell cycle. This study, probably the first detailed screening of the drug for its genotoxicity, shows that Fen is moderately clastogenic and a DNA damaging agent in vivo.

Item Type:Article
Source:Copyright of this article belongs to John Wiley and Sons.
Keywords:Chromosome Aberrations; Sister Chromatid Exchange (SCE); DNA Damage; ANOVA; Trend Test
ID Code:39026
Deposited On:06 May 2011 09:30
Last Modified:06 May 2011 09:30

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