Efeitos toxicogenéticos e toxicogenômicos do Isotiocianato de Alila (óleo de mostarda) em linhagens celulares de carcinoma de bexiga

• Autor(a) principal: Sávio, André Luiz Ventura [UNESP]
• Data de Publicação: 2014
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://hdl.handle.net/11449/113891
• topic: Bexiga - Câncer; Expressão gênica; Isotiocianatos; Crucifera; Toxicologia genética; Plantas - Toxinas; Óleos vegetais; Plant toxins

Compounds obtained from fruits, vegetables and essential oils have been widely used to treat many diseases. The allyl isothiocyanate (AITC), also known as mustard essential oil, is found in plants of the cruciferous family and is abundant in the mustard seeds. Due to its high bioavailability in urine, AITC has been considered as a promising antineoplastic agent against bladder cancer. Therefore, the aims of this study were to investigate the toxicogenetic and toxicogenomic effects of AITC in the wild-type (RT4) and in a mutant (T24) TP53 bladder transitional carcinoma cell lines. AITC was tested at concentrations of 0.005, 0.0625, 0.0725, 0.0825, 0.0925, 0.125 and 0.25 μM in the cytotoxicity and cell and clonogenic survival assays; in the comet and micronucleus assays, flow cytometry, apoptosis and gene expression (ANLN, BAX, BCL-2, CDK-1, SMAD4, S100P e TP53) evaluations the concentrations of 0.005; 0.0625; 0.0725; 0.0825 e 0.0925 μM were used. The results showed increased primary DNA damage in T24 (0.005, 0.0625, 0.0725, 0.0825 and 0.0925 μM) and RT4 (0.0725, 0.0825 and 0.0925 μM) cells. However, no significant difference was detected in the frequency of micronucleated cells. A significant increase of cells at sub-G1 phase (0.0625, 0.0725 and 0.0825 μM) and significant decrease at S phase (0.005, 0.0625, 0.0725 and 0.0825 μM) were observed in RT4 cells after AITC treatments. In T24 cells, an increased sub-G1 rate (0.0725 and 0.0825 μM) and cell cycle arrest at G2 phase (0.0625, 0.0725 and 0.0825 μM) were detected. Furthermore, it was observed increased apoptosis and necrosis rates and increase of S100P and BAX and decrease of BCL-2 expression in the wild type TP53 cells. For the mutated TP53 cell line, increased expression of BCL-2, BAX and ANLN and decreased expression S100P were observed. No change was detected for the SMAD4 and CDK-1 genes. In conclusion, AITC was able to reach DNA and induce primary damage in both bladder ...