4 resultados para MYELOMONOCYTIC LEUKEMIA
em Repositório Científico do Instituto Politécnico de Lisboa - Portugal
Resumo:
Four ruthenium(II) complexes with the formula [Ru(eta(5)-C(5)H(5))(PP)L][CF(3)SO(3)], being (PP = two triphenylphosphine molecules), L = 1-benzylimidazole, 1; (PP = two triphenylphosphine molecules), L = 2,2'bipyridine, 2; (PP = two triphenylphosphine molecules), L = 4-Methylpyridine, 3; (PP = 1,2-bis(diphenylphosphine) ethane), L = 4-Methylpyridine, 4, were prepared, in view to evaluate their potentialities as antitumor agents. The compounds were completely characterized by NMR spectroscopy and their crystal and molecular structures were determined by X-ray diffraction. Electrochemical studies were carried out giving for all the compounds quasi-reversible processes. The images obtained by atomic force microscopy (AFM) suggest interaction with pBR322 plasmid DNA. Measurements of the viscosity of solutions of free DNA and DNA incubated with different concentrations of the compounds confirmed this interaction. The cytotoxicity of compounds 1234 was much higher than that of cisplatin against human leukemia cancer cells (HL-60 cells). IC(50) values for all the compounds are in the range of submicromolar amounts. Apoptotic death percentage was also studied resulting similar than that of cisplatin. (C) 2010 Elsevier Inc. All rights reserved.
Resumo:
Formaldehyde (FA) ranks 25th in the overall U.S. chemical production, with more than 5 million tons produced each year. Given its economic importance and widespread use, many people are exposed to FA occupationally. Recently, based on the correlation with nasopharyngeal cancer in humans, the International Agency for Research on Cancer (IARC) confirmed the classification of FA as a Group I substance. Considering the epidemiological evidence of a potential association with leukemia, the IARC has concluded that FA can cause this lymphoproliferative disorder. Our group has developed a method to assess the exposure and genotoxicity effects of FA in two different occupational settings, namely FAbased resins production and pathology and anatomy laboratories. For exposure assessment we applied simultaneously two different techniques of air monitoring: NIOSH Method 2541 and Photo Ionization Detection Equipment with simultaneously video recording. Genotoxicity effects were measured by cytokinesis-blocked micronucleus assay in peripheral blood lymphocytes and by micronucleus test in exfoliated oral cavity epithelial cells, both considered target cells. The two exposure assessment techniques show that in the two occupational settings peak exposures are still occurring. There was a statistical significant increase in the micronucleus mean of epithelial cells and peripheral lymphocytes of exposed individuals compared with controls. In conclusion, the exposure and genotoxicity effects assessment methodologies developed by us allowed to determine that these two occupational settings promote exposure to high peak FA concentrations and an increase in the micronucleus mean of exposed workers. Moreover, the developed techniques showed promising results and could be used to confirm and extend the results obtained by the analytical techniques currently available.
Resumo:
Worldwide formaldehyde is manipulated with diverse usage properties, since industrial purposes to health laboratory objectives, representing the economic importance of this chemical agent. Therefore, many people are exposed to formaldehyde environmentally and/or occupationally. Considering the latter, there was recommended occupational exposure limits based on threshold mechanisms, limit values and indoor guidelines. Formaldehyde is classified by the International Agency for Cancer Research (IARC) as carcinogenic to humans (group 1), since a wide range of epidemiological studies in occupational exposure settings have suggested possible links between the concentration and duration of exposure and elevated risks of nasopharyngeal cancer, and others cancers, and more recently, with leukemia. Although there are different classifications, such as U.S. EPA that classified formaldehyde as a B1 compound, probable human carcinogen under the conditions of unusually high or prolonged exposure, on basis of limited evidence in humans but with sufficient evidence in animals. Formaldehyde genotoxicity is well-known, being a direct-acting genotoxic compound positively associated for almost all genetic endpoints evaluated in bacteria, yeast, fungi, plants, insects, nematodes, and cultured mammalian cells. There are many human biomonitoring studies that associate formaldehyde occupational exposure to genomic instability, and consequently possible health effects. Besides the link with cancer, also other pathologies and symptoms are associated with formaldehyde exposure, namely respiratory disorders such as asthma, and allergic contact dermatitis. Nowadays, there are efforts to reduce formaldehyde exposure, namely indoor. Europe and United States developed more strict regulation regarding formaldehyde emissions from materials containing this agent. Despite the regulations and restrictions, formaldehyde still continues to be difficult to eliminate or substitute, being biomonitoring an important tool to control possible future health effects.
Resumo:
A new family of "Fe-II(eta(5)-C5H5)" half sandwich compounds bearing a N-heteroaromatic ligand coordinated to the iron center by a nitrile functional group has been synthesized and fully characterized by NMR and UV-Vis spectroscopy. X-ray analysis of single crystal was achieved for complexes 1 and 3, which crystallized in the monoclinic P2(1)/c and monoclinic P2(1)/n space groups, respectively. Studies of interaction of these five new complexes with plasmid pBR322 DNA by atomic force microscopy showed very strong and different types of interaction. Antiproliferative tests were examined on human leukemia cancer cells (HL-60) using the MTT assay, and the IC50 values revealed excellent antiproliferative activity compared to cisplatin. (C) 2014 Elsevier B.V. All rights reserved.