Genotoxic studies in hypertensive and normotensive rats treated with amiodarone.

Amiodarone, a benzofuran derivative, is a very effective antiarrhythmic medication, but has potential to cause side effects. Although its cytotoxicity potential is very well-known, there are few reports about its genotoxicity effects. Since amiodarone has not been investigated in genotoxicity studies, and the spontaneously hypertensive rat (SHR) is a well-characterized model for hypertension, the aim of the present study was to perform cytogenetic analysis on chromosome aberrations in bone marrow cells of SHRs and normotensive Wistar-Kyoto rats (WKYs) that received oral amiodarone treatment for 4 weeks. Amiodarone activity was also monitored using electrocardiograms. The presence of bradycardia in amiodarone-treated rats confirmed that this drug was really active. Metaphase analysis on bone marrow cells showed that there were significant differences in total chromosomal damage and percentage abnormal metaphase between WKY and SHR negative controls. In the SHR negative control, the frequencies of basal chromosomal aberrations and abnormal metaphases were significantly higher (p<0.05). There were high numbers of chromosomal aberrations in all amiodarone-treated groups, compared with negative controls. In amiodarone-treated groups, the most frequent chromosomal aberration was chromatid breaks. More chromosomal aberrations were found in WKYs that received amiodarone, with a statistically significant difference in comparison with negative controls (p<0.05). However, in SHR rats there was no significant difference between the amiodarone and negative groups regarding chromosomal damage induction. These results showed that treatment with amiodarone was genotoxic in WKYs, but not in SHRs. Further studies are needed to confirm whether amiodarone is genotoxic or efficient and harmless, among humans undergoing therapy.

Cytogenetic analysis in lymphocytes from workers occupationally exposed to low levels of ionizing radiation.

The aim of the present study was to perform a cytogenetic analysis in peripheral lymphocytes of 36 individuals occupationally exposed to low levels of ionizing radiation, and compare the results with 36 controls, using the chromosomal aberrations test (CA), sensitivity to bleomycin and cytokinesis-blocked micronucleus assay (MN). The frequencies of CA/100 cells observed for the exposed workers were not significantly higher than in controls (P>0.05). The mean break/cell (b/c) for the controls and exposed workers was 0.59±0.39 and 0.57±0.29, respectively (P>0.01). The MN frequencies were significantly increased (P<0.01) in exposed workers (6.13±3.18) in comparison with controls (5.11±3.85). The mean MN was also statistically higher in the non-smoker exposed when compared with non-smoker controls, 5.80±3.09 and 5.15±4.08, respectively (P<0.01). The cytogenetic analysis of MN proved to be the most sensitive biological marker to assess the cellular response to low levels of irradiation.

Hemoglobinas anormais em sangue de cordão umbilical / Abnormal hemoglobins in umbilical cord blood

Hemoglobin pathologies are heterogeneous groups of recessively inherited disorders, which include thalassemias and falciform-related diseases. A falciform-related Illness is a generic term for the family of hemoglobin pathologies characterized by the presence of hemoglobin S (Hb S). Brazil is a country with a significant ethnical admixture, in which the colonization process played a great role on the spread of abnormal genes, specifically thalassemias and sickle cell disease. The mutations that give origin to these diseases are specific to some regions; in many cases determined by ethnical and geographical distributions. This knowledge serves as a basis for control programs and genetic counseling. This study evaluated the presence of abnormal hemoglobins in newborn children using alkaline electrophoresis in cellulose acetate and shows their incidence among the Uberaba population. Control samples of Hb FS and Hb FC were used, as well as Hb AF. From a total of 506 newborn children, 485 presented with normal hemoglobins and 21 presented with abnormal hemoglobins. Prevention of hemoglobin pathologies is important to detect heterozygotes and to explain about the alteration that they carry and the probability of transmission to their offspring.

Deficiência de G-6-PD nos recém-nascidos de Uberaba, MG: [carta ao editor] / G-6-PD deficiency in neonates in Uberaba, MG: [letter to editor]

Glucose 6-Phosphate desidrogenase (G-6-PD) is a cytoplasmicenzyme present in all cells whose main function, in erythrocytes, isto protect against oxygen free radicals, through the production ofNADPH. G-6-PD deficiency is the most common enzymopathy inhuman beings, affecting about 2 to 3% of the population worldwide.The necessity of neonatal screening of G-6-PD has been discussedin Brazil because of this high frequency. We used the Intercientíficatest, which utilizes G-6-PD and in the presence of NAD, catalyzesthe oxidation of G-6-P to 6-fosfogluconato. The NADPH producedis kinetically measured at 340 nm, correcting the enzymatic activityaccording to the concentration of the Hb at 405 nm. As controls,lyophilized erythrocytes were used. The samples were collected fromthe umbilical cord in EDTA. Of the 506 samples that were analyzed,44 presented activity of the G-6-PD of more than 17.1 U/gHb (91.5%)were compatible with normal enzymatic activity; 33 (females) and01 (male) with activity between 5.7 and 17.1 U/gHb (6.5%) werecompatible with partial deficiency and 10 (male) with less than 5.7U/gHb enzymatic activity (1.9%), compatible with total deficiency.With these results we concluded that partial and total deficiency ofG-6-PD in the city of Uberaba is 8.4%.

Evaluation of the clastogenicity and anticlastogenicity of the carotenoid bixin in human lymphocyte cultures.

Carotenoids are regarded as effective antioxidants, antimutagenic and anticarcinogenic agents. Annatto, a red-yellow extract obtained from seeds of Bixa orellana L. is a mixture of several carotenoids and one of them bixin (BXN), is known as its major coloring compound. Studies on BXN clastogenicity and anticlastogenicity in cultured human lymphocytes have not been reported so far. Therefore, the present study was undertaken to investigate the ability of BXN to induce chromosomal aberrations in human lymphocytes in vitro and to examine the possible anticlastogenic effect of this carotenoid in chromosomal damage induced by the clastogen cisplatin (cDDP). Human blood samples were obtained from six healthy, non-smoking volunteers; two females and four males aged 18-35 years. The concentrations of BXN (1.0; 2.5; 5.0 or 10 microg/mL) tested in combination with cDDP were established on the basis of mitotic index (MI) measurements. The data showed that BXN was not cytotoxic or clastogenic, when compared to untreated control. A marked decrease in the MI values compared to the untreated control and an increased percentage of aberrant metaphases was seen in all cultures treated with cDDP. The carotenoid efficiency in reducing the inhibitory effect of cDDP on lymphocyte MI is concentration-dependent. Cultures simultaneously treated with BXN and cDDP showed a statistically significant reduction in total chromosomal aberrations and aberrant metaphases. In our experiments, BXN may have acted as an antioxidant by intercepting free radicals generated by cDDP. The data obtained in the present study suggest that dietary carotenoids may act as protective agents against clastogenic effects of antitumor agents. However, extensive studies are necessary to elucidate the mechanism of action of BXN before its therapeutic use.