In vitro assessment of cytotoxic, genotoxic and mutagenic effects of antimalarial drugs artemisinin and artemether in human lymphocytes.

Artemisinin is a substance extracted from the Chinese plant Artemisia annua L. widely used in natural medicine for the treatment of various diseases. Artemether is a substance synthesized from artemisinin, and both drugs are commonly administered in the treatment of malaria. Although considered effective antimalarial drugs, very little is known about the genotoxic, cytotoxic and mutagenic effects of these drugs. Therefore, in the present study, we evaluated the genotoxic, mutagenic and cytotoxic effects of artemisinin (12.5, 25 and 50 µg/mL) and artemether (7.46; 14.92 and 29.84 µg/mL) in cultured human lymphocytes using the comet assay, the micronucleus test and the cytotoxicity assay for detection of necrosis and apoptosis by acridine orange/ethidium bromide staining. Our results showed a significant increase (p < 0.05) in the rate of DNA damage measured by comet assay and in the micronucleus frequency after treatment with both drugs. It was also observed that only artemisinin induced a statistically significant increase (p < 0.05) in the number of lymphocytes with death by necrosis 48 h after treatment. The results demonstrated that these two drugs induce mutagenic, genotoxic and cytotoxic effects in cultured human lymphocytes. Our data indicate the need for caution in the use of such drugs, since genotoxic/mutagenic effects may increase the risk of carcinogenesis.

Cytogenetic characteristics of patients with signs and symptoms of myelodysplastic syndromes in the State of Pará, Brazil.

The myelodysplastic syndromes (MDS) are clonal hematopoietic diseases characterized by medullary dysplasia, cytopenias, and frequent evolution to acute myeloid leukemia. In 1982, the French-American-British (FAB) group proposed a classification for the MDS, based on morphological characteristics of peripheral blood and of the bone marrow. Later, cytogenetics proved to be a useful tool for the refinement of prognosis, through the use of the International Prognosis Score System (IPSS), as well as through evidence of clonality. Recently, the World Health Organization (WHO) proposed a new classification for the MDS, based on significant modifications of the FAB proposal, with the inclusion of chromosome analysis. A cytogenetic analysis was made of 17 patients with symptoms of MDS in the State of Para, based on WHO recommendations, and application of the IPSS. Good metaphases were obtained for 13 patients; 12 had a normal karyotype and only one had a clonal abnormality, del(3)(p25). The genes related to neoplastic processes that have been mapped to 3p are: XPC in 3p25.1 and FANCD2 and VHL in 3p25-26. Four patients had classic symptoms of MDS; in the rest the possibility of MDS was excluded or several months of observation before diagnosis were recommended. Among those with MDS, it was not possible to apply IPSS and WHO recommendations, because fundamental data were lacking, specifically the medullary blast and ring sideroblast counts. We advocate the implementation of routine cytogenetic analyses for the study of MDS, especially in patients with moderate hematopoietic dysplasia.

Síndromes mielodisplásicas: revisão dos esquemas de classificação / Myelodysplastic syndromes: classification schemes review

Introdução: As síndromes mielodisplásicas (SMD) são doenças clonais das células-tronco hematopoiéticas caracterizadas por hematopoiese ineficiente e freqüente evolução para leucemia mielóide aguda. Em 1982, o Grupo Franco-Americano-Britânico (FAB) propôs classificação para as SMD, baseada em características morfológicas no sangue periférico e medula óssea. Recentemente a organização Mundial de Saúde (OMS) publicou uma classificação revisada das SMD, baseada em modificações significantes da proposta FAB. Objetivo: Enfocar as principais diferenças entre os dois esquemas referidos de classificação. Método: Material pesquisado no banco de dados da Biblioteca Nacional de Medicina e do Centro Nacional para Informação em Biotecnologia dos Estados Unidos, com os termos: "síndromes "mielodisplásicas", "câncer", "classificação", "prognóstico", "revisão", "FAB", "OMS". Foram selecionados apenas artigos publicados em in-ês entre 1976 e 2004. Considerações Finais: A classificação da OMS das SMD foi construí da a partir do bem sucedido esquema FAB, da qual clínicos e patologistas estão familiarizados, e suas mudanças incluem dados citogenéticos e o refinamento dos critérios de diagnóstico. Contudo, como todos os esquemas de classificação, proposta da OMS deve ser considerada um trabalho em progressão e, à medida que forem acumuladas evidências sobre o significado de lesões genéticas específicas e características clínicas, revisões serão necessárias

Investigation of single strand conformational alterations of the TP53 gene in epithelial hyperplasias of the breast

Generally, benign breast lesions behave as innocuous and limited proliferations, but sometimes they can represent pre-cancerous diseases. The practical importance of epithelial hyperplasias studies is related to their potential for malignant transformation. The TP53 tumor supressor gene suffers the greatest number of mutations in human cancer Using single strand conformational polymorphism, we did a mutation screening in exons 5 to 8 of the TP53 gene in the tumoral tissues of five patients with epithelial hyperplasias of the breast. The obtained results do not show any polymorphism that indicates mutation. The lack of mutation indicates that this gene is not involved in the initial process of malignization, strengthening the hypothesis that mutations on TP53 gene are a late event in the breast carcinogenesis.