Potentiation by caffeine of the frequencies of chromosomal aberrations induced by chronic exposure to fenfluramine in mice.
Fenfluramine (Fen), an amphetamine-derivative widely used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice for assessing its clastogenic potentials. Concentrations of 0.75, 1.50 and 5.0 mg Fen/kg body weight (b.w.) were administered orally for the study. Long-term treatment for 21 days showed dose-dependent significant increase in chromosomal aberrations on the 8th day. A significant decrease in aberration levels was seen in the late treatment period. Caffeine alone produced dose- and duration-dependent clastogenicity at doses of 2.0, 4.0 and 6.0 mg/kg b.w. when given by gavage. Using caffeine post-treatment (4.0 and 6.0 mg/kg b.w.) 2 h after Fen application, a strong synergism could be seen in the late treatment period as shown by the dose-response curves and by statistical analysis using the principle of least squares. The results support the hypothesis that prolonged Fen application induces dose-dependent increase in post-replication repair and caffeine enhanced toxicity by inhibiting repair process(es). The study suggests that Fen is a clastogen and since caffeine may have a synergistic effect, it should be avoided during treatment.
Sen
S
S
Centre for Advanced Study in Cell and Chromosome Research, University of Calcutta, India.
Agarwal
K
K
Mukherjee
A
A
Sharma
A
A
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology*; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005277:Fenfluramine / Q000633:toxicity*; D008297:Male; D051379:Mice; D009153:Mutagens / Q000633:toxicity*
D009153:Mutagens; D005277:Fenfluramine; D002110:Caffeine