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.

Activity satellite association and polymorphism of Ag stained nucleolus organizer regions (Ag+ NORs) in lymphocytes from women with cervical uterine cancer.

Thirty five female patients with different stages of neoplastic lesions: cervical intraepithelial neoplasia (CIN) or dysplasia (CIN I and CIN II), in situ carcinoma (CIS), and adenocarcinoma, and 27 healthy women (controls) were studied to determine the activity, satellite association, and polymorphism of Ag stained nucleolus organizer regions (Ag+ NORs) in acrocentric chromosomes in metaphases obtained from peripheral blood lymphocytes. For each person, 25 to 50 metaphases stained with ammoniacal silver technique were scored. The average number of Ag+ NORs was higher in women with adenocarcinoma (7.66 +/- 0.72) than in controls (6.65 +/- 0.74). Non-associated chromosomes showing Ag+ NORs were found more frequently in patients (5.85 +/- 0.88) than in controls (4.81 +/- 0.67). Patients aged 30-39 and 60 or more had an increase of Ag+ NORs (7.99 +/- 1.04, and 7.81 +/- 0.71) with respect to their controls (6.36 +/- 0.052 and 6.17 +/- 0.88), but the frequency of satellite association showed lower values in 50-59 year-old patients (0.75 +/- 0.08) than in controls (1.02 +/- 0.19). The most frequent association in patients was the large type (patients = 38.96%, controls = 30.49%). The partial association showed higher values (6.49%) than controls (2.44%). Otherwise, the spherical association was more frequent for controls (37.80%) than for patients (28.57%). All these differences were statistically significant (p < 0.05). The frequency of Ag+ NORs and the type of polymorphism of satellite association could be related to the neoplastic process, while the frequency of satellite association and of polymorphism of Ag+ NORs seems to be irrelevant.

Risk estimation of ABO and Rho(D) incompatibility in persons with mono- and polyphyletic surnames in Monterrey, Mexico. Comparison with other Mexican populations.

ABO and Rh(o)(D) blood groups were determined in 3813 males and females affiliated with the Instituto Mexicano del Seguro Social (IMSS) who are residents of the Monterrey Metropolitan Area (MMA) in northeastern Mexico. They were selected by their monophyletic or polyphyletic surnames. The ABO and Rh(o)(D) blood group phenotypes and gene frequencies were determined and based upon these, the risk of incompatibilities was estimated for both marriages (MI) and maternal-fetal incompatibility (MFI). These were compared with those estimated for other populations of residents in the MMA, and in other locations in Mexico, as well as with the two most important ancestral populations, Spanish and Tlaxcaltecan Mexican Indians, with the hypothesis that the percent of risk of ABO and Rh(o)(D) MI and MFI are greater in the population with monophyletic surnames than those with polyphyletic surnames. It was found that for persons with monophyletic and polyphyletic surnames, as well as for the other populations in the MMA and other places in Mexico, their ABO and Rho(D) MI and MFI percent of risk are intermediate to the ones estimated for their ancestry. The percentages of MI and MFI are higher for the persons with monophyletic than for the ones with polyphyletic surnames, other populations from the MMA and those from other locations in Mexico. The risks are higher when the similarity with Spanish increases and are lower when their similarities with the Mexican Indians increase.

Relationships by isonymy between persons with monophyletic and polyphyletic surnames from the Monterrey metropolitan area, Mexico.

Three thousand two hundred eleven males and females who resided and were interviewed in the Monterrey metropolitan area in northeastern México were selected for having 1 of 10 common selected surnames as either their patronymic or matronymic name. Five of the names are considered monophyletic and five are considered polyphyletic. Because each individual has two surnames, information about the name complementary to the selected surname was analyzed using isonymy methods (1) to see the effect of immigration on the genetic composition of the population and (2) to determine the isonymy, the relationship by isonymy within and between the persons with monophyletic and polyphyletic surnames. The percentages of the most common complementary surnames, the coefficients of relationship by isonymy of surnames for a selected surname, and the coefficients of relationship between the selected surnames are higher in the monophyletic than in the polyphyletic surnames, indicating that the persons with monophyletic names still conserve some customs of the founders that possibly increase their degree of endogamy. Perhaps these indicators are inversely related to migration, indicating that the monophyletic surnames have been more stable in Monterrey since it was colonized.