Photoexcited fullerenes

MiyataN, Yamakoshi Y, Nakanishi I (2000) Reactive species responsible for biological actions of photoexcited fullerenes. J Pharm Soc Jpn 120 1007-1016. 

Yamakoshi Y, Sueyoshi S, Miyata N (1999) Biological activity of photoexcited fullerene. Bull Natl Inst Health Sci 117 50-60. 

Yamakoshi Y, UmezawaN, Ryu A, Arakane K, MiyataN, Goda Y, Masumizu T, Nagano T (2003) Active oxygen species generated from photoexcited fullerene (C60) as potential medicines 02- versus 102. J Am Chem Soc 125 12803-12809. 

Effects of Photoexcited Fullerene C60-Composites in Normal and Transformed Cells... 

Abstract The supramolecular composites containing fullerenes C60 immobilized at nanosilica were used for the design of the molecular systems that can be an effective agent in cancer photodynamic therapy (PDT). In particular, it was shown that photoexcited fullerene C60-containing composites decrease viability of transformed cells, intensify the process of lipid peroxidation (LPO) in cell membranes and accumulation of low-molecular weight DNA fragments, and also decrease the activity of electron-transport chain of mitochondria. 

The aim of the work was evaluation of the ability of photoexcited fullerene C60 and synthesized fullerene C60-containing composites to generate reactive oxygen species (ROS) and to perform comparative analysis of the state of the cells of two types (normal ones - thymocytes, and malignant ones - the cells of ascite Erhch carcinoma [EAC] and leucosis L1210) by such indexes as viability, content of LPO products, MTT test, and DNA fragmentation upon incubation in the presence of photoexcited fullerene C60. 

The influence of photoexcited fullerene C60 on viability of thymocytes, EAC, and L1210 cells was studied after 24 h of incubation, considering the content of viable cells at incubation as 100% (Table 6.1). After irradiation of fullerenes C60 in the cell medium, significant decrease in the content of viable cells in the suspension of thymocytes was not registered, whilst the number of viable malignant cells decreased. Upon the presence of photoexcited fullerene C60 in incubation medium, the number of viable EAC cells decreased by 20%, and L1210 by 12%, while in the... 

Taking into account that ROS produced by irradiated fullerenes C60 may act only in the radius of their short diffusion existence, one may suppose that cytotoxic effect is determined by the interaction of fullerene C60 with the surface of cells and initiation of chain reactions of free radical peroxidation in membranes. That is why the influence of photoexcited fullerene C60 on the course of LPO process was studied and evaluated by the content of generated primary (diene conjugates) and final (Schiff bases) products. The content of diene conjugates in thymocytes was 17.7 4.2, inEAC cells was 21.1 1.3, andinL1210 was 12.8 3.1 nM/mg protein, and Schiff bases -56 7.9,46.5 4.5, and 36.6 4.6 rel. units/mg protein, respectively, and did not alter during 1 h incubation of the cells. 

In the case of photoexcited fullerenes C60 and fullerene C60-containing composites in incubation medium of thymocytes, the indexes of LPO did not alter compared to the control too (Fig. 6.2A). Upon incubation of EAC cells in the presence of photoexcited samples of fullerenes, the decrease in the content of diene conjugates by 35% in the presence of fullerene C60 and by 20% in the presence of fullerene C60-composite-1 and fullerene C60-composite-2 was observed (Fig. 6.2B). The presence of photoexcited samples of fullerenes in the suspension of L1210 cells influenced LPO indexes only in the presence of fullerene C60-composite-2, when the content of diene conjugates increased by 35% (Fig 6.2C). 

It has been shown that the influence of photoexcited fullerene C60 on the processes of free-radical oxidation depends on the type of the cell and on the composition of composite. So, in thymocytes in the presence of photoexcited fullerene C60 as well as fullerene C60-containing composites, the content of primary and final LPO products did not alter compared to the control. In malignant cells the intensification of LPO processes was registered, and its level depends on the type of cells. So, in thymocytes in the presence of photoexcited fullerene C60 in suspension of EAC cells the decrease in the content of diene conjugates simultaneously with the increase in the... 

Literature data on cytotoxic effects of photoexcited fullerene C60 are controversial. In the studies on transformed B-lymphocytes of Raji fine, phototoxic action of water-soluble carboxy-C60 was not revealed even upon its concentration of 5 x 10 5 M (Irie et al., 1996). In the study (Kamat et al., 2000) damaging effect of fullerenes C60 in dependence on intensity of irradiation toward CHO cells has been demonstrated. Using microsomal fraction of rat liver that was treated with C -cyclodextrin complex, it was shown that already in 5-30 min after UV-irradiation the accumulation of LPO products occurs that is suppressed by antioxidants like ascorbic acid and a-tocopherol. Similar effect of fullerenes C60 has been revealed in microsomal fraction of the cells of ascitic sarcoma 180 (Kamat et al., 2000). 

Upon 20 h of incubation of thymocyte suspension in the presence of photoexcited fullerene C60, the part of the degraded DNA increased insignificantly. As one may see from Fig. 6.4a, upon the presence of fullerenes C60, the content of PDN increased by 10%, fullerene C60-composite-l by 14%, and fullerene C60-composite-2 by 13% compared to the control. 

As one may see from the data presented in Fig. 6.5a, upon the presence of photoexcited samples of fullerenes in incubation medium of thymocytes, no significant changes in the rate of MTT reduction were observed during 5 h. Upon the presence of photoexcited fullerene C60 in incubation medium of suspension of L1210 cells,... 

Use of photoexcited fullerenes (i.e., the singlet or triplet excited state) widens the scope of electron-transfer reactions. This assumption is because excitation of fullerenes enhances both the electron-acceptor and -donor behavior of the photoexcited fullerenes. For example, the triplet excited state of C o, which is formed by efficient intersystem crossing (i.e. with a quantum yield close to unity) [18, 19] has a reduction potential of E°red = 1.14 V relative to the SCE [18, 19]. This potential is clearly more positive than the reduction potential of the ground state (—0.43 V) [20]. Thus, the triplet excited state of Ceo can be reduced with a variety of organic compounds yielding the Cgo radical anion and the oxidized donor [18]. 

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