Mutagenic activity of diazepam evaluated by in vivo cytogenetic tests.
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.
Leal Garza
C H
CH
Centro de Investigación Biomédica del Noroeste, IMSS, Monterrey, Nuevo León, Mexico. cleal@academ01.mty.itesm.mx
Valenciano Cedillo
G G
GG
Rojas Alvarado
M A
MA
Cortes Gutierrez
E I
EI
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D003975:Diazepam / Q000633:toxicity*; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D012854:Sister Chromatid Exchange
D003975:Diazepam