{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T07:10:55Z","timestamp":1768806655372,"version":"3.49.0"},"reference-count":61,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2000,2,1]],"date-time":"2000-02-01T00:00:00Z","timestamp":949363200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxicology and Applied Pharmacology"],"published-print":{"date-parts":[[2000,2]]},"DOI":"10.1006\/taap.1999.8834","type":"journal-article","created":{"date-parts":[[2002,9,18]],"date-time":"2002-09-18T22:01:25Z","timestamp":1032386485000},"page":"50-59","source":"Crossref","is-referenced-by-count":46,"title":["Hypoxia-Dependent Retinal Toxicity of Bioreductive Anticancer Prodrugs in Mice"],"prefix":"10.1006","volume":"163","author":[{"given":"Alan E.","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William R.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1006\/taap.1999.8834_RF1","first-page":"516","article-title":"Oxygen distribution in the macaque retina","volume":"34","author":"Ahmed","year":"1993","journal-title":"Invest. Opthalmol. Vis. Sci."},{"key":"10.1006\/taap.1999.8834_RF2","series-title":"Handbook of Physiology. The Cardiovascular System IV","first-page":"1001","article-title":"Circulation in the eye","author":"Bill","year":"1984"},{"key":"10.1006\/taap.1999.8834_RF3","first-page":"523","article-title":"Retinal oxygen tension and the electroretinogram during arterial occlusion in the cat","volume":"36","author":"Braun","year":"1995","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1006\/taap.1999.8834_RF4","first-page":"542","article-title":"Oxygen consumption in the inner and outer retina of the cat","volume":"36","author":"Braun","year":"1995","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1006\/taap.1999.8834_RF5","first-page":"793","article-title":"Effects of light intensity and retinal pigmentation on nitro-imidazole-induced retinal degeneration in rats","volume":"24","author":"Breider","year":"1996","journal-title":"Toxicol. Pathol."},{"key":"10.1006\/taap.1999.8834_RF6","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1177\/019262339802600207","article-title":"Retinal degeneration in rats induced by CI-1010, a 2-nitroimidazole radiosensitizer","volume":"26","author":"Breider","year":"1998","journal-title":"Toxicol. Pathol."},{"key":"10.1006\/taap.1999.8834_RF7","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1177\/019262339802600509","article-title":"Nitro-imidazole radiosensitizer-induced toxicity in cynomolgus monkeys","volume":"26","author":"Breider","year":"1998","journal-title":"Toxicol. Pathol."},{"key":"10.1006\/taap.1999.8834_RF8","first-page":"941","article-title":"Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma","volume":"56","author":"Brizel","year":"1996","journal-title":"Cancer Res."},{"key":"10.1006\/taap.1999.8834_RF9","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0360-3016(97)00101-6","article-title":"Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck","volume":"38","author":"Brizel","year":"1997","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"10.1006\/taap.1999.8834_RF10","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1038\/bjc.1993.220","article-title":"SR 4233 (tirapazamine): A new anticancer drug exploiting hypoxia in solid tumours","volume":"67","author":"Brown","year":"1993","journal-title":"Br. J. Cancer"},{"key":"10.1006\/taap.1999.8834_RF11","first-page":"1408","article-title":"The unique physiology of solid tumors: Opportunities (and problems) for cancer therapy","volume":"58","author":"Brown","year":"1998","journal-title":"Cancer Res."},{"key":"10.1006\/taap.1999.8834_RF12","first-page":"7745","article-title":"Potentiation by the hypoxic cytotoxin SR 4233 of cell killing produced by fractionated irradiation of mouse tumors","volume":"50","author":"Brown","year":"1990","journal-title":"Cancer Res."},{"key":"10.1006\/taap.1999.8834_RF13","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S1053-4296(96)80033-6","article-title":"Hypoxia specific cytotoxins in cancer therapy","volume":"6","author":"Brown","year":"1996","journal-title":"Semin. Radiat. Oncol."},{"key":"10.1006\/taap.1999.8834_RF14","first-page":"302","article-title":"Definitive evidence for hypoxic cells influencing cure in cancer therapy","volume":"37","author":"Bush","year":"1978","journal-title":"Br. J. Cancer"},{"key":"10.1006\/taap.1999.8834_RF15","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/BF00437469","article-title":"Regulation of VEGF\/VPF expression in tumor cells: Consequences for tumor growth and metastasis","volume":"15","author":"Claffey","year":"1996","journal-title":"Cancer Metastasis Rev."},{"key":"10.1006\/taap.1999.8834_RF16","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/0360-3016(92)90872-F","article-title":"Dual function nitroimidazoles less toxic than RSU 1069: Selection of candidate drugs for clinical trial (RB 6145 and\/or PD 130908)","volume":"22","author":"Cole","year":"1992","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"10.1006\/taap.1999.8834_RF17","first-page":"S32","article-title":"Recent developments in the design of bioreductive drugs","volume":"74","author":"Denny","year":"1996","journal-title":"Br. J. Cancer"},{"key":"10.1006\/taap.1999.8834_RF18","first-page":"4633","article-title":"Tumor-specific, schedule-dependent interaction between tirapazamine (SR 4233) and cisplatin","volume":"53","author":"Dorie","year":"1993","journal-title":"Cancer Res."},{"key":"10.1006\/taap.1999.8834_RF19","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/379088a0","article-title":"Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours","volume":"379","author":"Graeber","year":"1996","journal-title":"Nature"},{"key":"10.1006\/taap.1999.8834_RF20","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/BF00588242","article-title":"Mechanisms of blood-brain barrier breakdown","volume":"33","author":"Greenwood","year":"1991","journal-title":"Neuroradiol."},{"key":"10.1006\/taap.1999.8834_RF21","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/(SICI)1520-6823(1997)5:5<235::AID-ROI4>3.0.CO;2-Z","article-title":"Bioreductive alkylating agent porfiromycin in combination with radiation therapy for the management of squamous cell carcinoma of the head and neck","volume":"5","author":"Haffty","year":"1997","journal-title":"Radiat. Oncol. Invest."},{"key":"10.1006\/taap.1999.8834_RF22","first-page":"4509","article-title":"Association between tumor hypoxia and malignant progression in advanced cancers of the uterine cervix","volume":"56","author":"H\u00f6ckel","year":"1996","journal-title":"Cancer Res."},{"key":"10.1006\/taap.1999.8834_RF23","doi-asserted-by":"crossref","first-page":"139","DOI":"10.2307\/3577429","article-title":"Tumor radiosensitization by nicotinamide: A result of improved perfusion and oxygenation","volume":"118","author":"Horsman","year":"1989","journal-title":"Radiat. Res."},{"key":"10.1006\/taap.1999.8834_RF24","first-page":"29","article-title":"Effect of deficiences in DNA repair on the toxicity of mitomycin C and porfiromycin to CHO cells under aerobic and hypoxic conditions","volume":"3","author":"Hughes","year":"1991","journal-title":"Cancer Commun."},{"key":"10.1006\/taap.1999.8834_RF25","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1021\/jm00171a040","article-title":"Synthesis and evaluation of \u03b1[[(2-haloethyl)amino]methyl]-2-nitro-1H-imidazole-1-ethanols as prodrugs of \u03b1-[(1-aziridinyl)methyl]-2-nitro-1H-imidazole-1-ethanol (RSU-1069) and its analogues which are radiosensitizers and bioreductively activated cytotoxins","volume":"33","author":"Jenkins","year":"1990","journal-title":"J. Med. Chem."},{"key":"10.1006\/taap.1999.8834_RF26","first-page":"3992","article-title":"Unusual oxygen concentration dependence of toxicity of SR 4233, a hypoxic cell toxin","volume":"53","author":"Koch","year":"1993","journal-title":"Cancer Res."},{"key":"10.1006\/taap.1999.8834_RF27","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1085\/jgp.88.4.521","article-title":"Effects of light and darkness on oxygen distribution and consumption in the cat retina","volume":"88","author":"Linsenmeier","year":"1986","journal-title":"J. Gen. Physiol."},{"key":"10.1006\/taap.1999.8834_RF28","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/BF02764309","article-title":"Electrophysiological consequences of retinal hypoxia","volume":"228","author":"Linsenmeier","year":"1990","journal-title":"Graefe's Arch. Clin. Exp. Ophthalmol."},{"key":"10.1006\/taap.1999.8834_RF29","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1085\/jgp.99.2.177","article-title":"Oxygen distribution and consumption in the cat retina during normoxia and hypoxemia","volume":"99","author":"Linsenmeier","year":"1992","journal-title":"J. Gen. Physiol."},{"key":"10.1006\/taap.1999.8834_RF30","first-page":"5655","article-title":"Oxygen and exposure kinetics as factors influencing the cytotoxicity of porfiromycin, a mitomycin C analogue, in Chinese hamster ovary cells","volume":"48","author":"Marshall","year":"1988","journal-title":"Cancer Res."},{"key":"10.1006\/taap.1999.8834_RF31","first-page":"1667","article-title":"Tissue oxygen during a critical development period controls the death and survival of photoreceptors","volume":"38","author":"Maslim","year":"1997","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1006\/taap.1999.8834_RF32","first-page":"631","article-title":"Photoreceptor apoptosis induced by a single systemic administration of N-methyl-N-nitrosourea in the rat retina","volume":"148","author":"Nakajima","year":"1996","journal-title":"Am. J. Pathol."},{"key":"10.1006\/taap.1999.8834_RF33","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/j.1440-1827.1997.tb04511.x","article-title":"Morphologic characteristics of N-methyl-N-nitrosourea-induced retinal degeneration in C57BL mice","volume":"47","author":"Nambu","year":"1997","journal-title":"Pathol. International."},{"key":"10.1006\/taap.1999.8834_RF34","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0167-8140(96)91811-3","article-title":"Pretreatment oxygenation predicts radiation response in advanced squamous cell carcinoma of the head and neck","volume":"41","author":"Nordsmark","year":"1996","journal-title":"Radiother. Oncol."},{"key":"10.1006\/taap.1999.8834_RF35","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/bjc.1995.106","article-title":"Detection of hypoxia be measurement of DNA damage in individual cells from spheroids and murine tumours exposed to bioreductive drugs. 2. RSU. 1069","volume":"71","author":"Olive","year":"1995","journal-title":"Br. J. Cancer"},{"key":"10.1006\/taap.1999.8834_RF36","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1016\/0006-2952(87)90239-5","article-title":"Induction of DNA crosslinks in vitro upon reduction of the nitroimidazole-aziridines RSU-1069 and RSU-1131","volume":"36","author":"O'Neill","year":"1987","journal-title":"Biochem. Pharmacol."},{"key":"10.1006\/taap.1999.8834_RF37","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/S1053-4296(96)80032-4","article-title":"Modification of hypoxia-induced radioresistance in tumors by the use of oxygen and sensitizers","volume":"6","author":"Overgaard","year":"1996","journal-title":"Semin. Radiat. Oncol."},{"key":"10.1006\/taap.1999.8834_RF38","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1021\/jm00040a009","article-title":"Hypoxia-selective antitumor agents. 9. Structure-activity relationships for hypoxia-selective cytotoxicity among analogues of 5-[N,N-bis(2-chloroethyl)amino]-2,4-dinitrobenzamide","volume":"37","author":"Palmer","year":"1994","journal-title":"J. Med. Chem."},{"key":"10.1006\/taap.1999.8834_RF39","first-page":"625","article-title":"Alkylating property of nitro-imidazole radiosensitizers is required for induction of murine retinal degeneration","volume":"33","author":"Parker","year":"1996","journal-title":"Vet. Pathol."},{"key":"10.1006\/taap.1999.8834_RF40","first-page":"541","article-title":"Enzymology of tirapazamine metabolism: A review","volume":"13","author":"Patterson","year":"1998","journal-title":"Anti-Cancer Drug Des."},{"key":"10.1006\/taap.1999.8834_RF41","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/BF00689805","article-title":"Rationale for the use of aliphatic N-oxides of cytotoxic anthraquinones as prodrug DNA binding agents: A new class of bioreductive agent","volume":"12","author":"Patterson","year":"1993","journal-title":"Cancer Metastasis Rev."},{"key":"10.1006\/taap.1999.8834_RF42","article-title":"Single dose intravenous toxicity of CI-1010, a cytotoxic radiosensitizing nitroimidazole derivative, in rats","author":"Pilcher","year":"1996","journal-title":"Fundam. Appl. Toxicol."},{"key":"10.1006\/taap.1999.8834_RF43","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1097\/00006982-199515040-00011","article-title":"Retinal oxygen distribution. Its role in the physiopathology of vasoproliferative microangiopathies","volume":"15","author":"Pournaras","year":"1995","journal-title":"Retina"},{"key":"10.1006\/taap.1999.8834_RF44","doi-asserted-by":"crossref","unstructured":"Pournaras, C. J.1996. Autoregulation of ocular blood flow. In Ocular Blood Flow (H. J. Kaiser, J. Flammer, and P. Hendrickson, Eds.), pp. 40\u201350. Karger, Basel.","DOI":"10.1159\/000425031"},{"key":"10.1006\/taap.1999.8834_RF45","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/S0360-3016(98)00302-2","article-title":"Bioreductive therapies: An overview of drugs and their mechanisms of action","volume":"42","author":"Rauth","year":"1998","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"10.1006\/taap.1999.8834_RF46","doi-asserted-by":"crossref","first-page":"100","DOI":"10.2307\/3577481","article-title":"Preclinical studies of porfiromycin as an adjunct to radiotherapy","volume":"116","author":"Rockwell","year":"1988","journal-title":"Radiat. Res."},{"key":"10.1006\/taap.1999.8834_RF47","doi-asserted-by":"crossref","first-page":"623","DOI":"10.3109\/02713688709025223","article-title":"Cytochrome P450, drug metabolising enzymes and arachadonic acid metabolism in bovine ocular tissues","volume":"6","author":"Schwartzman","year":"1987","journal-title":"Current Eye Res."},{"key":"10.1006\/taap.1999.8834_RF48","first-page":"362","article-title":"Rationale for the selection of PD 144872, the R isomer of RB 6145, for clinical development as a radiosensitizer","volume":"34","author":"Sebolt-Leopold","year":"1993","journal-title":"Proc. Am. Assoc. Cancer Res."},{"key":"10.1006\/taap.1999.8834_RF49","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0167-8140(97)00224-7","article-title":"Potentiation of cisplatin activity by the bioreductive agent tirapazamine","volume":"47","author":"Siemann","year":"1998","journal-title":"Radiother. Oncol."},{"key":"10.1006\/taap.1999.8834_RF50","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/bjc.1994.357","article-title":"Oxygen dependence of the cytotoxicity and metabolic activation of 4-alkylamino-5-nitroquinoline bioreductive drugs","volume":"70","author":"Siim","year":"1994","journal-title":"Br. J. Cancer"},{"key":"10.1006\/taap.1999.8834_RF51","first-page":"1888","article-title":"Monitoring communications between photoreceptors and pigment epithelial cells: Effects of \u201cmild\u201d systemic hypoxia","volume":"28","author":"Steinberg","year":"1987","journal-title":"Invest. Opthalmol. Vis. Sci."},{"key":"10.1006\/taap.1999.8834_RF52","first-page":"519","article-title":"Bioreductive drugs into the next mellenium","volume":"13","author":"Stratford","year":"1998","journal-title":"Anti-Cancer Drug Des."},{"key":"10.1006\/taap.1999.8834_RF53","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1038\/bjc.1997.227","article-title":"The distribution and expression of the two isoforms of DNA topoisomerase II in normal and neoplastic human tissues","volume":"75","author":"Turley","year":"1997","journal-title":"Br. J. Cancer"},{"key":"10.1006\/taap.1999.8834_RF54","first-page":"141","article-title":"Assessment of blood-retinal barrier integrity","volume":"10","author":"Vinores","year":"1995","journal-title":"Histol. Histopathol."},{"key":"10.1006\/taap.1999.8834_RF55","first-page":"454a","article-title":"Survival benefit from tirazone (tirapazamine) and cisplatin in advanced non-small cell lung cancer (NSCLC) patients: Final results from the international phase III CATAPULT 1 trial","volume":"17","author":"vonPawel","year":"1998","journal-title":"Proc. Am. Soc. Clin. Oncol."},{"key":"10.1006\/taap.1999.8834_RF56","first-page":"4473","article-title":"Repair of DNA and chromosome breaks in cells exposed to SR 4233 under hypoxia or to ionizing radiation","volume":"52","author":"Wang","year":"1992","journal-title":"Cancer Res."},{"key":"10.1006\/taap.1999.8834_RF57","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/0360-3016(86)90262-2","article-title":"Studies on the toxicity of RSU-1069","volume":"12","author":"Whitmore","year":"1986","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"10.1006\/taap.1999.8834_RF58","series-title":"Cancer Biology and Medicine","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/978-94-009-0385-2_4","article-title":"Tumour hypoxia: Challenges for cancer chemotherapy","author":"Wilson","year":"1992"},{"key":"10.1006\/taap.1999.8834_RF59","first-page":"634","article-title":"Quantitative oxygen dependence (K values) for bioreductive drug cytotoxicity","volume":"35","author":"Wilson","year":"1994","journal-title":"Proc. Am. Assoc. Cancer Res."},{"key":"10.1006\/taap.1999.8834_RF60","first-page":"663","article-title":"Radiation-activated prodrugs as hypoxia-selective cytotoxins: Model studies with nitroarylmethyl quaternary salts","volume":"13","author":"Wilson","year":"1998","journal-title":"Anti-Cancer Drug Des."},{"key":"10.1006\/taap.1999.8834_RF61","first-page":"483","article-title":"N-Methyl-N-nitrosourea-induced photoreceptor apoptosis in the mouse retina","volume":"10","author":"Yuge","year":"1996","journal-title":"In Vivo"}],"container-title":["Toxicology and Applied Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X99988348?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X99988348?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,5,7]],"date-time":"2019-05-07T04:26:58Z","timestamp":1557203218000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041008X99988348"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,2]]},"references-count":61,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2000,2]]}},"alternative-id":["S0041008X99988348"],"URL":"https:\/\/doi.org\/10.1006\/taap.1999.8834","relation":{},"ISSN":["0041-008X"],"issn-type":[{"value":"0041-008X","type":"print"}],"subject":[],"published":{"date-parts":[[2000,2]]}}}