Showing papers by "Lusânia Maria Greggi Antunes published in 2007"

Modulatory effects of the antioxidant ascorbic acid on the direct genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

Abstract: In this study two different crosses involving the wing cell markers mwh and flr3 (standard (ST) cross and high bioactivation (HB) cross, the latter being characterized by a high constitutive level of cytochrome P450 which leads to an increased sensitivity to a number of promutagens and procarcinogens) were used to investigate the modulatory effects of ascorbic acid (AA) combined with the antitumor agent doxorubicin (DXR) in Drosophila melanogaster. We observed that the two different concentrations of AA (50 or 100 mM) had no effect on spots frequencies, while DXR treatments (0.2 or 0.4 mM) gave positive results for all types of spots, when compared to negative control. For marker-heterozygous (MH) flies, a protective effect was observed with the lower concentration of AA (50 mM) that was able to statistically decrease the frequency of spots induced by DXR (0.2 mM), while an enhanced frequency of spots induced by DXR was observed with the higher concentration of AA (100 mM), when compared to DXR treatment (p < 0.05). These results suggest that AA may interfere with free radicals generated by DXR and with other possible reactive metabolites. The efficiency of AA in protecting the somatic cells of D. melanogaster against mutation and recombination induced by DXR is dependent on the dose used and the protection is directly related to the activity of cytochrome P450 enzymes.

Acetylsalicylic acid exhibits anticlastogenic effects on cultured human lymphocytes exposed to doxorubicin.

Abstract: Acetylsalicylic acid (ASA) is a non-steroidal anti-inflammatory drug (NSAID) with many pharmacological properties, such as anti-inflammatory, antipyretic and analgesic. Many studies have suggested the possible efficiency of ASA and other NSAIDs in preventing cancer. ASA could also have antimutagenic and antioxidant properties. The aim of this study was to investigate the possible clastogenic and anticlastogenic effects of different concentrations of ASA on doxorubicin-induced chromosomal aberrations in human lymphocytes. Human blood samples were obtained from six healthy, non-smoking volunteers; and the chromosomal aberration assay was carried out using conventional techniques. The parameters analyzed were mitotic index, total number of chromosomal aberrations and percentage of aberrant metaphases. The concentrations of ASA (25, 50 or 100 microg/mL) tested in combination with DXR (0.2 microg/mL) were established on the basis of the results of the mitotic index. The treatment with ASA alone was neither cytotoxic nor clastogenic (p>0.01). In lymphocyte cultures treated with different combinations of ASA and DXR, a significant decrease in the total number of chromosome aberrations was observed compared with DXR alone (p<0.01). This protective effect of ASA on DXR-induced chromosomal damage was obtained for all combinations, and it was most evident when ASA was at 25.0 microg/mL. In our experiments, ASA may have acted as an antioxidant and inhibited the chromosomal damage induced by the free radicals generated by DXR. The identification of compounds that could counteract the free radicals produced by doxorubicin could be of possible benefits against the potential harmful effects of anthracyclines. The results of this study show that there is a relevant need for more investigations in order to elucidate the mechanisms underlying the anticlastogenic effect of ASA.

Identificação dos polimorfismos do gene XRCC1 em pacientes com anemia falciforme

Abstract: Sickle cell disease (SCD) is an inherent disorder caused by asingle nucleotide substitution The great variability in clinical andhematological features of SCD provides a challenge in theunderstanding of the pathophysiological mechanisms leading tothe disease The identification of DNA polymorphisms cancontribute to understand the role of the different biomarkers andtheir relationships with the extremely variable clinical manifestationof SCD In order to contribute to the identification of polymorphismsin SCD, we proposed to study the distribution of the DNA repairgene XRCC1 in SCD patients and healthy control individuals Ourresults indicate that the polymorphisms of the XRCC1 variantalleles 399Gln and 194Trp were not statistically different betweenthe groups studied We observed a tendency for the prevalence ofthe Gln/Gln genotype in SCD patients The results from ongoinginvestigations with other polymorphisms have been elucidatingthe role of such biomarkers and their relationships with the clinicalmanifestation of SCD Rev bras hematol hemoter 2006;