Natural and recombinant interferons (IFNs) have already demonstrated therapeutic efficacy, including cytogenetic remissions, in patients with chronic myelocytic leukemia (CML). We investigated at the level of ligand-receptor interaction the question whether heterogeneity of receptor number or affinity might contribute to primary or secondary treatment failures in CML. We therefore analyzed IFN-gamma and IFN-alpha receptor expression and regulation during treatment with recombinant IFN-gamma and IFN-alpha in 15 patients with advanced CML. We found no difference in number or affinity of constitutively expressed IFN-gamma receptors (mean 1,100) and, on average, a 30% reduction of IFN-alpha receptors (mean 750) on peripheral blood mononuclear cells (PBMNC) of patients with chronic or accelerated CML as compared to mature granulocytes and/or bone marrow cells of healthy controls, which express on average 1,050 and 1,100 IFN-gamma and IFN-alpha receptors, respectively. While IFN-gamma receptor expression on PBMNC is not influenced upon treatment with rIFN-gamma, there is a substantial downregulation of IFN-alpha receptors in the course of rIFN-alpha therapy. Our data also show a differential pattern of receptor downregulation between patients achieving complete hematologic remission (CHR) (4 out of 12) compared with patients with partial hematologic remission (PHR) and non-responders. We conclude that differences in IFN receptor number cannot explain primary or secondary treatment failures. However, the differential ligand induced downregulation of IFN-alpha receptors in patients achieving CHR compared to those with PHR or non-responders suggest a prospective value of IFN-alpha receptor determination.

The cyanotoxin cylindrospermopsin (CYN) is the second biggest cause of poisoning worldwide, both in humans and animals. Although CYN primarily affects the aquatic environments and can be absorbed in fishes by multiple routes, data reporting its toxicity and mechanism of action are still scarce in this group. Using P. reticulata as model species, it was evaluated whether CYN promotes mutagenic and genotoxic effects in different fish target tissues. Adult females were exposed in a static way to 0 (control), 0.5, 1.0, and 1.5 μg L −1 of pure CYN for 24 and 96 hours. For the first time, DNA damage was detected in fish brain after CYN exposition. In brain cells, a concentrationresponse DNA damage was observed for both exposure times, suggesting a direct or indirect action of CYN in neurotoxicity. For the liver cells, 96 hours caused an increase in DNA damage, as well the highest percentage of DNA in the tail was reached when used 1.5 μg L −1 of CYN. In peripheral blood cells, an increase in DNA damage was observed for all tested concentrations after 96 hours. In erythrocytes, micronuclei frequency was higher at 1.5 μg L −1 treatment while the erythrocyte nuclear abnormalities (ENA) frequency was significantly higher even at the lowest CYN concentration. Such data demonstrated that acute exposition to CYN promotes genotoxicity in the brain, liver, and blood cells of P. reticulata, as well mutagenicity in erythrocytes. It rises an alert regarding to the toxic effects of CYN for aquatic organisms as well as for human health.

Introdução: A espécie Cochlospermum regium (Mart. & Schr.) Pilger é consideravelmente utilizada na medicina popular para o tratamento de doenças infectoparasitárias e carcinogênicas, porém ainda não se tem conhecimento do risco em utiliza-la, sendo necessário avaliações de mutagenicidade. A espécie vegetal Allium cepa tem sido amplamente observada e utilizada para avaliar o potencial de mutagenicidade e citotoxicidade de plantas medicinais e isolados devido sua alta sensibilidade e sua excelente correlação com variados marcadores farmacogenéticos. Com a utilização crescente de plantas medicinais pela população, é de grande importância a avaliação dos efeitos de mutagenicidade e citotoxicidade dessas substâncias para manter a integridade da saúde das pessoas. Objetivo: O objetivo deste trabalho foi de avaliar o potencial mutagênico e citotóxico de diferentes concentrações do extrato de C. regium. Metodologia: Para a análise foi utilizado o sistema teste Allium cepa (Asparaginales, Alliaceae). Para realização da técnica de Allium cepa utilizou-se o protocolo segundo Fieskejo & Grant (1985). Resultados e discussão: O extrato de C. regium, nas concentrações utilizadas, exibiu efeito citotóxico paralisando as células em profáse e não mostrou efeito mutagênico. Conclusão: Concluindo que a planta C. regium utilizada como planta medicinal pela comunidade, apresenta efeito citotóxico, podendo causar efeitos colaterais e maléficos para quem fizer o uso indiscriminado do extrato para o tratamento de alguns tipos de doenças, porém para a confirmação destes efeitos necessita-se de maior investigação.Palavras- chave: Allium cepa, Mutagenicidade, Citotoxicidade, Alterações cromossômicas.

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