[Reactive species responsible for biological actions of photoexcited fullerenes].
Fullerene (C60, C70, 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, cancer-initiation, and cell-toxicity. A newly synthesized C60 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 C60 in water in the presence of NADH as a reductant and molecular oxygen resulted in the formation of O2.-, which was detected by the EPR spin-trapping method. Formation of O2.- was also evidenced by the direct observation of a characteristic signal of O2.- by the use of a low-temperature EPR technique at 77 K. On the other hand, no formation of 1O2 was observed by the use of TEMP as a 1O2 trapping agent. No near-IR luminescence of 1O2 was also observed in the aqueous C60/PVP/O2 system. These results suggest that photoinduced bioactivities of the PVP-solubilized fullerene are caused not by 1O2, but by reduced oxygen species (O2.-, .OH) which are generated by the electron-transfer reaction of C60.- with molecular oxygen.
Miyata
N
N
Division of Organic Chemistry, National Institute of Health Sciences, Tokyo, Japan.
Yamakoshi
Y
Y
Nakanishi
I
I
D000818:Animals; D002244:Carbon / Q000494:pharmacology / Q000633:toxicity; D002273:Carcinogens; D004247:DNA / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D037741:Fullerenes; D008027:Light; D016296:Mutagenesis / Q000187:drug effects; D009243:NAD; D010100:Oxygen; D017319:Photosensitizing Agents; D011205:Povidone; D017382:Reactive Oxygen Species; D012995:Solubility; D019097:Spin Trapping; D014867:Water
D002273:Carcinogens; D037741:Fullerenes; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D014867:Water; D009243:NAD; C069836:fullerene C70; D002244:Carbon; D004247:DNA; D011205:Povidone; C069837:fullerene C60; D010100:Oxygen