フラーレンの光増感生物作用に関与する反応活性種の解析

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Fullerene (C_<60>, C_<70>, etc.) is an effective photosensitizer and its utilization as a pharmacophore for photo-chemotherapy of tumors has received considerable attention. We developed a method to solubilize fullerenes into water with polyvinylpyrrolidone (PVP) as a detergent. By using thus prepared aqueous fullerene solutions, we have clarified a series of biological activities of fullerene under photoirradiation which include DNA-cleavage, hemolysis, mutagenicity, cancerinitiation, and cell-toxicity. A newly synthesized C_<60> derivative with an acridine moiety as a DNA-chelating function showed much more effective DNA-cleaving activity in the presence of NADH. Visible-light irradiation of PVP-solubilized C_<60> in water in the presence of NADH as a reductant and molecular oxygen resulted in the formation of O_2・^-, which was detected by the EPR spin-trapping method. Formation of O_2・^-was also evidenced by the direct observation of a characteristic signal of O_2・^-by the use of a low-temperature EPR technique at 77 K. On the other hand, no formation of ^1O_2 was observed by the use of TEMP as a ^1O_2 trapping agent. No near-IR luminescence of ^1O_2 was also observed in the aqueous C_<60>/PVP/O_2 system. These results suggest that photoinduced bioactivities of the PVP-solubilized fullerene are caused not by ^1O_2,but by reduced oxygen species (O_2・^-, ・OH) which are generated by the electron-transfer reaction of C_<60>・^- with molecular oxygen
社団法人日本薬学会の論文
2000-10-01

フラーレンの光増感生物作用に関与する反応活性種の解析

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