Francisca da Luz Dias

Potentiation by turmeric and curcumin of γ-radiation-induced chromosome aberrations in Chinese hamster ovary cells

The effect of turmeric and curcumin, two natural antioxidants, on the frequencies of chromosome aberrations induced in Chinese hamster ovary (CHO) cells by gamma-radiation was investigated. Cells were treated with three concentrations of each drug, turmeric (100, 250, and 500 microg/ml) and curcumin (2.5, 5, and 10 microg/ml), and then irradiated (2.5 Gy) during different phases of the cell cycle. Turmeric was not clastogenic by itself, whereas curcumin at 10 microg/ml enhanced the chromosomal damage frequency. Neither of the two antioxidants showed protective effect against the clastogenicity of gamma-radiation. Instead, an obvious increase in the frequencies of chromosome aberrations was observed when turmeric at 500 microg/ml was associated with gamma-radiation during G2/S phase, and curcumin at 10 microg/ml plus gamma-radiation during S and G2/S phases of the cell cycle. The results clearly indicate the exacerbated effect of turmeric and curcumin on radiation-induced clastogenicity, suggesting that these antioxidants are also potentiating agents depending on the experimental conditions.

Modulatory effects of curcumin on the chromosomal damage induced by doxorubicin in Chinese hamster ovary cells

Curcumin, a natural phenolic compound, is gaining importance as a free radical scavenger. This study was undertaken to investigate the modulatory effects of curcumin on the chromosomal damage induced by the antitumoral doxorubicin (DXR), a known free radical generator, in Chinese hamster ovary cells in culture. Cells were treated with three concentrations of curcumin (2.5, 5, or 10 microg/ml) and then treated with DXR (1.0 microg/ml) during different phases of the cell cycle. The results show that curcumin induces chromosomal damage in CHO at the highest concentration when compared to the untreated control. Neither treatment with curcumin shows a reduction in the clastogenicity of DXR. Instead, a statistically significant increase in the frequency of chromosomal damage was observed when the middle and the highest concentrations of curcumin were associated with DXR during the G1/S, S, and S/G2 phases of the cell cycle. The results clearly indicate the potentiating effect of curcumin on DXR-induced chromosomal damage.

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.

Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in Chinese hamster ovary cells

Antioxidantes de ocorrencia natural tem sido exaustivamente estudados quanto a sua capacidade de proteger organimos e celulas contra danos oxidativos. Muitos constituintes das plantas, incluindo curcuma e curcumina, parecem ser potentes antimutagenos e antioxidantes. Os efeitos de curcuma e curcumina na frequencia de aberracoes cromossomicas induzidas pelo agente radiomimetico bleomicina (BLM) foram investigados em celulas do ovario de hamster chines (CHO). Tres concentracoes de cada droga, curcuma (100, 250 e 500 mg/ml) e curcumina (2,5, 5,0 e 10 mg/ml), foram combinadas com BLM (10 mg/ml) em celulas CHO tratadas durante as fases G1/S, S ou G2/S do ciclo celular. Nem curcuma nem curcumina evitaram o dano cromossomico induzido pela BLM em fase alguma do ciclo celular. Ao contrario, a potenciacao da clastogenicidade da BLM pelo curcumina foi nitidamente observada em celulas tratadas durante as fases S e G2/S. A curcumina tambem se mostrou clastogenica na dose de 10 mg/ml nos protocolos de tratamento de 9 e 13 h. Contudo, o mecanismo exato pelo qual a curcumina produziu efeitos potenciadores e clastogenicos permanece desconhecido.

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.

Effects of H2O2, Fe2+ and Fe3+ on curcumin-induced chromosomal aberrations in CHO cells

The effects of H2O2, Fe2+ and Fe3+ on curcumin-induced clastogenicity were evaluated in CHO cells. Curcumin combined with H2O2 did not increase the chromosomal aberrations more than expected based on a simple additive effect. In contrast, the combination of curcumin-Fe significantly decreased the total number of chromosomal aberrations and the number of abnormal metaphases. The clastogenicity of curcumin may be related to its pro-oxidant properties and its ability to generate free radicals.

Sensitivity to cisplatin-induced mutations and elevated chromosomal aberrations in lymphocytes from sickle cell disease patients

Sickle cell disease (SCD) is an inherited disorder caused by a single nucleotide substitution in the β-globin gene. The clinical heterogeneity observed in SCD patients has been attributed to environmental and genetic factors. The patients are subjected to increased oxidative stress, particularly during vaso-occlusive crises and acute chest pain. Another possible cause of oxidative stress in SCD is the high concentration of iron in the patients’ plasma. The increase in oxidative stress could be a relevant risk factor for mutagenesis and carcinogenesis. Studies on the frequency of basal chromosomal aberrations in cultured lymphocytes from SCD patients have not been reported so far. In order to contribute to the understanding of the role of the different biomarkers and their relationship with the extremely variable clinical manifestation of SCD, we investigated the frequency of chromosome damage in peripheral lymphocytes from sickle cells patients and healthy controls. We found an increased frequency of chromosome damage and percentage of aberrant metaphases in these patients when compared with control subjects, even at basal values (p < 0.05). In the cytogenetic sensitivity assay, the results showed that these patients presented a marked decrease in the mitotic index values compared with healthy controls. Cisplatin-induced chromosomal damage in lymphocytes from these patients was significantly higher than the frequency measured in healthy controls. The results obtained in the present study showed that more investigations are needed in order to elucidate the susceptibility to genomic instability of SCD patients.

Hemoglobinas anormais em sangue de cordão umbilical

Abstract Hemoglobin pathologies are heterogeneous groups of recessivelyinherited disorders, which include thalassemias and falciform-related diseases. A falciform-related Illness is a generic term for thefamily of hemoglobin pathologies characterized by the presence ofhemoglobin S (Hb S). Brazil is a country with a significant ethnicaladmixture, in which the colonization process played a great role onthe spread of abnormal genes, specifically thalassemias and sicklecell disease. The mutations that give origin to these diseases arespecific to some regions; in many cases determined by ethnical andgeographical distributions. This knowledge serves as a basis forcontrol programs and genetic counseling. This study evaluated thepresence of abnormal hemoglobins in newborn children usingalkaline electrophoresis in cellulose acetate and shows their incidenceamong the Uberaba population. Control samples of Hb FS and HbFC were used, as well as Hb AF. From a total of 506 newbornchildren, 485 presented with normal hemoglobins and 21 presentedwith abnormal hemoglobins. Prevention of hemoglobin pathologiesis important to detect heterozygotes and to explain about the alterationthat they carry and the probability of transmission to their offspring.

Chromosome damage induced by DNA topoisomerase II inhibitors combined with g-radiation in vitro

Combined radiation and antineoplastic drug treatment have important applications in cancer therapy. In the present work, an evaluation was made of two known topoisomerase II inhibitors, doxorubicin (DXR) and mitoxantrone (MXN), with g-radiation. The effects of DXR or MXN on g-radiation-induced chromosome aberrations in Chinese hamster ovary (CHO) cells were analyzed. Two concentrations of each drug, 0.5 and 1.0 µg/ml DXR, and 0.02 and 0.04 µg/ml MXN, were applied in combination with two doses of g-radiation (20 and 40 cGy). A significant potentiating effect on chromosomal aberrations was observed in CHO cells exposed to 1.0 µg/ml DXR plus 40 cGy. In the other tests, the combination of g-radiation with DXR or MXN gave approximately additive effects. Reduced mitotic indices reflected higher toxicity of the drugs when combined with radiation.

Effect of taxol on chromosome aberrations induced by gamma radiation or by doxorubicin in Chinese hamster ovary cells

Combined therapy with radiation and chemotherapy has being increasingly used in cancer treatment. The effect of combinations of taxol (0.08 mg/ml) with doxorubicin (DXR, 0.5 or 1.0 mg/ml) or gamma radiation (20 or 40 cGy) was examined in two different treatment schedules (pretreatment or simultaneous treatment) using Chinese hamster ovary (CHO) cells treated at the G2 phase of the cell cycle. The results showed that taxol did not have a radiosensitizing effect on the chromosomal aberrations induced by gamma radiation nor did it have a potentiating effect on the chromosomal aberrations induced by DXR in CHO cells treated in the G2 phase of the cell cycle