Yeast protective response to arsenate involves the repression of the high affinity iron uptake system.

Arsenic is a double-edge sword. On the one hand it is powerful carcinogen and on the other it is used therapeutically to treat acute promyelocytic leukemia. Here we report that arsenic activates the iron responsive transcription factor, Aft1, as a consequence of a defective high-affinity iron uptake mediated by Fet3 and Ftr1, whose mRNAs are drastically decreased upon arsenic exposure. Moreover, arsenic causes the internalization and degradation of Fet3. Most importantly, fet3ftr1 mutant exhibits increased arsenic resistance and decreased arsenic accumulation over the wild-type suggesting that Fet3 plays a role in arsenic toxicity. Finally we provide data suggesting that arsenic also disrupts iron uptake in mammals and the link between Fet3, arsenic and iron, can be relevant to clinical applications.

Molecular targeting therapy against promyelocytic leukemia protein using arsenic acids in experimental intracranial medulloblastoma.

Our previous study using human Daoy medulloblastoma cells showed that the promyelocytic leukemia (PML) gene was significantly upregulated (2.5-fold) in cells positive to prominin-1 antigen (CD133), a possible marker for cancer initiating cells. Arsenic trioxide (As(2)O(3)) is known to degrade PML protein and has been used for the treatment of patients with acute PML. In the present study, the effect of PML targeting therapy with As(2)O(3) and cytarabine (Ara-C) on Daoy medulloblastoma cell proliferation was investigated. Daoy cells were pretreated with As(2)O(3) for 6 weeks. The As(2)O(3)-pretreated Daoy cells were cultured in medium containing Ara-C and cell viability was examined. Next, the As(2)O(3)-pretreated Daoy cells were inoculated into the nude mouse brain and the effect of Ara-C on the tumor size was evaluated. A significant increase in chemosensitivity to Ara-C was observed in the As(2)O(3)-pretreated Daoy cells in both in vitro and in vivo conditions. PML and CCND1 (cyclin D1) protein expression of Daoy medulloblastoma cells was downregulated by As(2)O(3) treatment. PML has been proposed as a novel therapeutic target to eradicate quiescent leukemia-initiating cells, and PML-expressing CD133-positive cells are similarly a potential therapeutic target of treatment for medulloblastoma.

Uptake and toxicity of hexafluoroarsenate in aquatic organisms.

The arsenic species hexafluoroarsenate has been described as a contaminant of surface waters of anthropogenic origin. Here, we undertake to identify the most sensitive biological receptor among several sentinel aquatic species used in eco-toxicological assessment and to understand toxicity in terms of internal dose. Therefore, a screening of short-term effects using different aquatic organisms (bacterium Vibrio fischeri, fish Danio rerio, crustacean Daphnia magna and green alga Desmodesmus subspicatus and Scenedesmus vacuolatus) was conducted. For most organisms tested, effects were not detectable even at very high hexafluoroarsenate concentrations (up to 9.6mM) and thus the ecotoxic potential was found to be low in comparison to other arsenic compounds. The only organisms showing a clear response were the unicellular green alga, e.g. S. vacuolatus with an EC(50) value of 1.12 mM (84 mg L(-1) As). A linear relationship between ambient and internal concentration was found for this organism with a slope of 1.63 x 10(-3). Therefore, the internal concentration which shows a significant effect, e.g. 20% of inhibition of reproduction, was found to occur at a relatively low internal dose of 0.98 microM. Moreover, no biotransformation products inside the algae could be detected using arsenic speciation analysis with HPLC-ICP-MS, thus biological effects must be attributed to the untransformed compound. We conclude that the very low uptake observed for hexafluoroarsenate may be interpreted as preventive against toxic effects for the organisms.

Os efeitos da radiaçäo laser arseneto de gálio (AsGa) sobre a regeneraçäo de tendöes em cäes / The effects of lasertherapy AsGa on canine tendon healing

Trinta cäes sem raça definida foram divididos em três grupos e submetidos à tenotomia e tenorrafia do tendäo calcâneo comum direito e esquerdo. No membro esquerdo foi efetuada aplicaçäo laser AsGa (4j/cm ao quadrado) para avaliar o processo cicatricial dos mesmos. Posteriormente, as articulaçöes do tarso foram imobilizadas durante 11 dias nos animais do grupo I (sacrificados nesta data) e 21 dias naqueles do grupo II (sacrificados aos 22 dias) e III (sacrificados aos 40 dias de evoluçäo pós-operatória). Os cäes do grupo III foram submetidos a caminhadas diárias de 30 minutos nas duas semanas seguintes para estimular a mobilidade do tendäo. A avaliaçäo clínica dos efeitos da terapia laser na funcionalidade dos membros foi feita através de exames físicos. Os tendöes foram avaliados à necropsia através de análise macroscópica e pelo estudo microscópico realizado em todos os segmentos aos 11 (grupo I), vinte e dois (grupo II) e quarenta dias (grupo III) de evoluçäo pós-operatória. O desempenho funcional do membro esquerdo nos animais do grupo III, exposto à radiaçäo laser mostrou-se melhor que no membro direito. Macroscopicamente os tendöes irradiados apresentaram melhor vascularizaçäo, menos aderências e cicatrizaçäo com melhor aparência estética que os tendöes testemunhos. Os estudos histológicos revelaram que o laser näo interferiu significativamente na produçäo de fibroblastos e na síntese de fibras colágenas