Enhancing potency of neopterin toward B-16 melanoma cell damage induced by UV-A irradiation and its possible application for skin tumor treatment.
The enhancing potency of the oxidized form of neopterin (NP) towards long-wavelength ultraviolet light (UV-A) induced cytotoxicity was examined in vitro using mouse melanoma (B-16) cells. A sufficient dose of UV-A irradiation was used to cause damage (measured in terms of reduced DNA synthesis) to about 30% of the irradiated cells. NP drastically enhanced the UV-A-induced cell damage, whereas the reduced form of neopterin (NPH4), which possesses a strong antioxidative activity, abolished the UV-A-induced cell damage in a dose-dependent manner. These data suggest that radical oxygen species (ROS) may be involved in UV-Ainduced B-16 cell damage. Among various radical scavengers examined, only catalase protected B-16 cells from UV-A-induced cell damage and also abolished the enhancing potency of NP, suggesting that hydrogen peroxide may mediate the cell damage. We obtained similar results in another experiment on B-16 cell damage induced by hydrogen peroxide instead of UV-A. In an in vitro analysis of the chemilumi-nescence induced by hydrogen peroxide, NP remarkedly enhanced the signal intensity at a high concentration, while NPH4 reduced the intensity in a dose-dependent manner. These results suggest that elevation of the hydrogen peroxide-mediated cytotoxicity by NP may be involved in its enhancing potency toward UVA-induced B-16 cell damage, and may also indicate the possible utility of the oxidized form of neopterin as an enhancer for UV-A-irradiation treatment of tumors.
Kojima
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S
Research Institute for Biosciences, Science University of Tokyo, Chiba, Japan.
Icho
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T
Mori
H
H
Arai
T
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D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000528:radiation effects / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D019798:Neopterin; D017382:Reactive Oxygen Species; D012878:Skin Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D014407:Tumor Cells, Cultured; D014467:Ultraviolet Therapy
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D001708:Biopterins; D019798:Neopterin; D006861:Hydrogen Peroxide