Digest Journal of Nanomaterials and Biostructures Vol. 6, No 4, October-December 2011, p.1543-1551 PROTECTIVE EFFECT OF FULLERENOL NANO PARTICLES ON COLON CANCER DEVELOPMENT IN DIMETHYLHYDRAZINE RAT MODEL MARTINA PERŠE * Institute of Pathology, Medical Experimental Centre, Medical Faculty, University of Ljubljana, Korytkova 2, 1000 Ljubljana Slovenia , RADE INJAC a , ALEKSANDAR DJORDJEVIC b , BORUT ŠTRUKELJ a , ANTON CERAR a Faculty of Pharmacy, Institute of Pharmaceutical Biology, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia b Faculty of Sciences, Department of Chemistry, University of Novi Sad, Trg Dositeja Obradovica 3, 21000 Novi Sad, Serbia Colorectal cancer (CRC) is one of the most common cancers world-wide, with highest incidence rates in western countries. In recent years, much effort has been dedicated in search for natural or pharmacological preventive agents, which would block or attenuate CRC process. In search for new pharmacological agent, the effects of fullerenol C 60 (OH) 24 nano particles (FNP) on liver oxidative status and promotion or progression phase of colorectal carcinogenesis in dimethylhydrazine-induced rat model of CRC were investigated. Our results demonstrate that FNP effectively inhibited formation of dysplastic aberrant crypt foci, which are regarded as early histopathological lesions in the pathogenesis of CRC. FNP treatment also improved activity of antioxidant enzymes in the liver. Since this was the first study investigating FNP effects on colon carcinogenesis further studies are needed to evaluate its protective effect also in other phases of carcinogenesis and to investigate whether its inhibitory activity was due to modulation of carcinogen-induced oxidative stress or another yet unknown anticarcinogenic activity. (Received July 28, 2011; accepted October 4, 2011) Keywords: colorectal cancer, fullerenol nano particles, oxidative stress, dimethylhydrazine 1. Introduction Colorectal cancer (CRC) is one of the most common cancers world-wide, with highest incidence rates in western countries [1]. In recent years, growing attention has been paid to environmental and food components, with the hope of identifying its preventive or carcinogenic effects [2,3]. Much effort has been dedicated in search for natural or pharmacological preventive agents, which would block or attenuate CRC process [4,5]. Colon carcinogenesis is a multistage process, involving multiple genetic and epigenetic changes that provide tumour cells with a selective advantage to expand their clones [6]. Recent evidence has indicated that the generation of reactive oxygen species (ROS) may play important role in the initiation, promotion and progression stages of carcinogenesis [7]. It has been already shown that vitamin E has antiproliferative property in cancer cell lines, while different natural antioxidants such as gallic acid [8], polyphenols [9], vitamin D [10], vitamin A [11] as well as pharmacological compounds like bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione (BDMCA) [12] have potential to inhibit CRC development in dimethylhydrazine (DMH) model. DMH rat model is well establish CRC animal model and possess many characteristics found in human sporadic CRC, which makes it an important tool for studying different aspects of step-wise development of CRC under defined experimental conditions [13]. DMH administration has been * Corresponding author: martina.perse@mf.uni-lj.si