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 treat ment of obesity, has been evaluated in vivo in the bone marrow cells o f Swiss albino mice for assessing its clastogenic potentials. Concentr ations of 0.75, 1.50 and 5.0 mg Fen/kg body weight (b.w.) were adminis tered orally for the study. Long-term treatment for 21 days showed dos e-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- depende nt clastogenicity at doses of 2.0, 4.0 and 6.0 mg/kg b.w. when given b y gavage. Using caffeine post-treatment (4.0 and 6.0 mg/kg b.w.) 2h af ter Fen application, a strong synergism could be seen in the late trea tment period as shown by the dose-response curves and by statistical a nalysis using the principle of least squares. The results support the hypothesis that prolonged Fen application induces dose-dependent incre ase in postreplication repair and caffeine enhanced toxicity by inhibi ting repair process(es). The study suggests that Fen is a clastogen an d since caffeine may have a synergistic effect, it should be avoided d uring treatment.