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10.1111/j.1349-7006.2000.tb00963.x http://scihub22266oqcxt.onion/10.1111/j.1349-7006.2000.tb00963.x C5926472!5926472!10804292     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=10804292&cmd=llinks): Failed to open stream: HTTP request failed! 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A Novel Class of Antitumor Prodrug, 1?(2??Oxopropyl)?5?fluorouracil (OFU001), That Releases 5?Fluorouracil upon Hypoxic Irradiation |pdf=|usr=}}{{10804292}} gab.com Text A Novel Class of Antitumor Prodrug, 1 (2 Oxopropyl) 5 fluorouracil (OFU001), That Releases 5 Fluorouracil upon Hypoxic Irradiation JO: Jpn J Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=10804292 #FOAvip We have been developing prodrugs of anticancer agents such as 5?fluorouracil (5?FU) that are activated by irradiation under hypoxic conditions via one?electron reduction. Among them, OFU001 [1?(2??oxopropyl)?5?fluorouracil] is a prototype radiation?activated prodrug. In this study, we investigated the radiation chemical reactivity and the biological effects of OFU001. This prodrug is presumed to release 5?FU through incorporation of hydrated electrons into the antibonding ?* orbital of the C(1?)?N(1) bond. Hydrated electrons are active species derived from radiolysis of water, but are readily deactivated by O2 into superoxide anion radicals () under conditions of aerobic irradiation. Therefore, 5?FU release occurs highly specifically upon irradiation under hypoxic conditions. OFU001 dissolved in phosphate buffer released 5?FU with a G?value (mol number of molecules that are decomposed or produced by 1 J of absorbed radiation energy) of 1.9�10?7 mol/ J following hypoxic irradiation, while the G?value for 5?FU release was 1.0�10?8 mol/J following aerobic irradiation. However, the G?values for decomposition of OFU001 were almost the same, i.e., 3.4�10?7 mol/J following hypoxic irradiation and 2.5�10?7 mol/J following aerobic irradiation. When hypoxically irradiated (7.5?30 Gy) OFU001 was added to murine SCCVII cells for 1?24 h, a significant cell?killing effect was observed. The degree of this cytotoxicity was consistent with that of authentic 5?FU at the corresponding concentrations. On the other hand, cytotoxicity was minimal when the cells were treated with aerobically irradiated or unirradiated OFU001. This compound had no radiosensitizing effect against SCCVII cells under either aerobic or hypoxic conditions when the drug was removed immediately after irradiation. Since hypoxia is generally most marked in tumors and irradiation is applied at the tumor site, this concept of prodrug design appears to be potentially useful for selective tumor treatment with minimal adverse effects of anticancer agents. Twit Text FOAVip A Novel Class of Antitumor Prodrug, 1 (2 Oxopropyl) 5 fluorouracil (OFU001), That Releases 5 Fluorouracil upon Hypoxic Irradiation ????Jpn J Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=10804292 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=10804292 #FOAvip English Wikipedia <ref>{{Cite pmid|10804292}}</ref> A Novel Class of Antitumor Prodrug, 1?(2??Oxopropyl)?5?fluorouracil (OFU001), That Releases 5?Fluorouracil upon Hypoxic Irradiation #MMPMID10804292 Shibamoto Y; Zhou L; Hatta H; Mori M; Nishimoto S Jpn J Cancer Res 2000[Apr]; 91 (4): 433-8 PMID10804292show ga We have been developing prodrugs of anticancer agents such as 5?fluorouracil (5?FU) that are activated by irradiation under hypoxic conditions via one?electron reduction. Among them, OFU001 [1?(2??oxopropyl)?5?fluorouracil] is a prototype radiation?activated prodrug. In this study, we investigated the radiation chemical reactivity and the biological effects of OFU001. This prodrug is presumed to release 5?FU through incorporation of hydrated electrons into the antibonding ?* orbital of the C(1?)?N(1) bond. Hydrated electrons are active species derived from radiolysis of water, but are readily deactivated by O2 into superoxide anion radicals () under conditions of aerobic irradiation. Therefore, 5?FU release occurs highly specifically upon irradiation under hypoxic conditions. OFU001 dissolved in phosphate buffer released 5?FU with a G?value (mol number of molecules that are decomposed or produced by 1 J of absorbed radiation energy) of 1.9�10?7 mol/ J following hypoxic irradiation, while the G?value for 5?FU release was 1.0�10?8 mol/J following aerobic irradiation. However, the G?values for decomposition of OFU001 were almost the same, i.e., 3.4�10?7 mol/J following hypoxic irradiation and 2.5�10?7 mol/J following aerobic irradiation. When hypoxically irradiated (7.5?30 Gy) OFU001 was added to murine SCCVII cells for 1?24 h, a significant cell?killing effect was observed. The degree of this cytotoxicity was consistent with that of authentic 5?FU at the corresponding concentrations. On the other hand, cytotoxicity was minimal when the cells were treated with aerobically irradiated or unirradiated OFU001. This compound had no radiosensitizing effect against SCCVII cells under either aerobic or hypoxic conditions when the drug was removed immediately after irradiation. Since hypoxia is generally most marked in tumors and irradiation is applied at the tumor site, this concept of prodrug design appears to be potentially useful for selective tumor treatment with minimal adverse effects of anticancer agents. �A Novel Class of Antitumor Prodrug, 1?(2??Oxopropyl)?5?fluorouracil (O(epmc).pdf DeepDyve Pubget Overpricing