BACKGROUND: Diazepam, one of the benzodiazepine group of tranquilizers, is used as an adjunctive drug for sedation and for relief of anxiety in the treatment of epilepsy. Suspicion has been aroused of a possible mutagenic and teratogenic effect of this drug, thus the potential for cancer development. METHODS: To analyze the mutagenic effect of diazepam, the micronuclei and sister chromatid exchange (SCE) tests were performed by in vivo techniques in the bone marrow of Balb-C mice after intraperitoneal drug administration. Sixty mice, 30 males and 30 females, were classified as negative control (n = 12), positive control (n = 12), and three groups were treated with diazepam (n = 36). All groups were matched by sex, and each mouse received a single intraperitoneal injection. Negative control group was injected with physiological saline, positive control group with mitomycin-C at a dose of 0.5 mg/kg of body weight. Treated groups received diazepam, one at 0.1, the other at 0.2, and the last, at 0.4 mg/kg. RESULTS: The results showed a significant increase in the frequency of micronucleated polychromatic erythrocytes at all doses tested for whole population in relation to negative control. The polychromatic/normochromatic erythrocyte ratio showed a significant decrease at doses of 0.1 and 0.4 mg/kg in relation to negative control. The frequency of SCE was significantly higher at doses of 0.2 and 0.4 mg/kg in relation to negative control, the male mice being those affected. CONCLUSIONS: It is concluded that diazepam showed mutagenic and genotoxic effects on bone marrow cells of mice and that it might represent a human health risk.
BACKGROUND:Diazepam, one of the benzodiazepine group of tranquilizers, is used as an adjunctive drug for sedation and for relief of anxiety in the treatment of epilepsy. Suspicion has been aroused of a possible mutagenic and teratogenic effect of this drug, thus the potential for cancer development. METHODS: To analyze the mutagenic effect of diazepam, the micronuclei and sister chromatid exchange (SCE) tests were performed by in vivo techniques in the bone marrow of Balb-C mice after intraperitoneal drug administration. Sixty mice, 30 males and 30 females, were classified as negative control (n = 12), positive control (n = 12), and three groups were treated with diazepam (n = 36). All groups were matched by sex, and each mouse received a single intraperitoneal injection. Negative control group was injected with physiological saline, positive control group with mitomycin-C at a dose of 0.5 mg/kg of body weight. Treated groups received diazepam, one at 0.1, the other at 0.2, and the last, at 0.4 mg/kg. RESULTS: The results showed a significant increase in the frequency of micronucleated polychromatic erythrocytes at all doses tested for whole population in relation to negative control. The polychromatic/normochromatic erythrocyte ratio showed a significant decrease at doses of 0.1 and 0.4 mg/kg in relation to negative control. The frequency of SCE was significantly higher at doses of 0.2 and 0.4 mg/kg in relation to negative control, the male mice being those affected. CONCLUSIONS: It is concluded that diazepam showed mutagenic and genotoxic effects on bone marrow cells of mice and that it might represent a human health risk.