Effects of Fullerenol C 60 (OH) 24 on Cytotoxicity Induced by Antitumor Drugs on Human Breast Carcinoma Cell Lines V. Kojić 1,a , D. Jakimov 1,b , G. Bogdanović 1,c and A. Đorđević 2,d 1 Institute of Oncology Sremska Kamenica, Experimental Oncology Department, Institutski put 4, 21204 Sremska Kamenica, Serbia and Montenegro 2 Department of Chemistry, Faculty of Science, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia and Montenegro a vex@EUnet.yu, b dimac@ptt.yu, c gordanab@ptt.yu, d dvadj@ptt.yu Keywords: Breast Cancer, C 60 (OH) 24 , Cell Line, Cisplatin, Cytogenetic Tests, Cytotoxicity Tests, Doxorubicin, Fullerenol, Genotoxicology, Taxol, Tiazofurin. Abstract. The aims of this paper were to investigate cell growth activity of fullerenol C 60 (OH) 24 , its modulating effect on antitumor drug-induced cytotoxicity, and genotoxic influence of fullerenol at nanomolar concentrations. Human breast cancer cell lines, MCF-7 and MDA-MB-231, were treated with fullerenol at concentrations from 0.9 to 3.9 μg/ml alone or simultaneously with antitumor drugs (doxorubicin, cisplatin, taxol, and tiazofurin; IC50 concentrations) for 2 hours. Growth inhibition was evaluated by colorimetric SRB assay after recovery period of 24, 48, and 96 hours. The genotoxic examination was performed using sister chromatid exchange test and micronucleus assay, at fullerenol concentration ranging from 1 to 5 μg/ml. The fullerenol alone mildly inhibits the growth of both cell lines. Simultaneous administration of fullerenol and antitumor drugs strongly suppressed antitumor drug-induced cytotoxicity. The rate of cytotoxicity inhibition depended on fullerenol concentration, type of antitumor drug and cell line. Protection against doxorubicin and cisplatin was more pronounced than against taxol and tiazofurin. Fullerenol was not found to be genotoxic to investigated cell lines. Introduction Since the discovery of fullerenes in 1985, C 60 has elicited intense interest and recent chemical studies have revealed a diverse reactivity of C 60 [1]. Chemical modification of fullerenes toward water-soluble derivatives [2] resulted in compounds exhibiting a variety of biological activities. Derivation of C 60 with hydroxyl groups opened a wide range of possible biomedical applications. Polyhidroxilated C 60 fullerene derivatives, fullerenols (C 60 (OH) X ), can be potential antioxidative agents and free radical scavengers in biological systems [3-6]. The results of our previous in vitro studies on several cell lines of human solid tumors show that fullerenol at nanomolar concentrations, continuously present in culture for 48 hours, induces low but transient inhibition of cell growth [7], modulates cell cycle of the human erytroleukaemia cells influencing both synthetic and mitotic cell cycle phase [8], and strongly suppresses antitumor drug induced cytotoxicity against human breast cancer cell lines [9]. Results also indicated that fullerenol exerts a cytostatic rather than a cytotoxic activity [8]. The effect of fullerenol on cell growth activity of doxorubicin, cisplatin, taxol and tiazofurin on human breast cancer cells was investigated. These cytostatics have various mechanisms of action. Doxorubicin and cisplatin are cell cycle phase nonspecific while taxol is M and tiazofurin is S cell cycle phase specific. For most of them, except for taxol, their toxic activity can be explained by formation of free radicals. Data relating genotoxic properties of water-soluble fullerenes are still insufficient. Several in vitro and in vivo studies on genotoxic activity of fullerene C 60 and fullerenol have not revealed any mutagenic or genotoxic effects [10]. Materials Science Forum Vol. 494 (2005) pp. 543-548 online at http://www.scientific.net © 2005 Trans Tech Publications, Switzerland Licensed to Bogdanovic (gordanab@ptt.yu) - Serbia-Montenegro All rights reserved. No part of the contents of this paper may be reproduced or transmitted in any form or by any means without the written permission of the publisher: Trans Tech Publications Ltd, Switzerland, www.ttp.net . (ID: 82.208.205.213-08/03/05,12:02:12)