Abstract
Abstract This study aims to evaluate the cellular effects of amino benzazolo [3,2- a] quinolinium drugs on normal lymphoblast cells and compare them to effects on A431 epitheloid carcinoma cells. The drugs under study are amino containing heterocyclic compounds possessing a positive charge that could facilitate their interaction with cell organelles specially mitochondria. The fluorescent properties could also facilitate observation of their cellular binding location. These compounds have also been demonstrated to have mutagenic and DNA binding capacity on A431 cancer cells. A431 and TK6 cells in culture where exposed for 48 hours to determine the IC50 dose, mitochondrial membrane permeability, ROS generation and fluorescent microscopy analysis of intracellular binding. IC50 was determined by trypan blue exclusion and mitochondrial membrane permeability applying the Nucleo counter 3000, JC-1 assay. For ROS determination the fluorescent dye 2,7-dichlorofluorescein diacetate (DCFH-DA) was applied. Determination of intracellular binding was performed applying confocal microscopy. In the TK6 normal lymphoblast cells the observed IC50 concentrations were as follow: ABQ38=310µM, and ABQ95=270µM. On A431 IC50s were as follows: ABQ38 = 32 µM and ABQ95 = 36 µM. Overall, normal TK6 demonstrated higher tolerance to the tested ABQS than A 431. Preliminary results on ROS generation indicated a stronger ROS release on A431 than on TK6 lymphoblast. Analysis of the effects of ABQS on the mitochondrial permeability where also consistent with the cytotoxicity observed, demonstrating higher levels of membrane permeability on treated tumor cells than on normal. Microscopy images of ABQS treated cells revealed location of these fluorescent compounds in organelles such as mitochondria and DNA. DNA fragmentation analyses are being implemented. This study presents preliminary evidence of an overall higher tolerance of normal TK6 lymphoblast to the tested fluorescent drugs in comparison to treated A431. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4474. doi:10.1158/1538-7445.AM2011-4474
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