PMID: 9547861Apr 21, 1998Paper

Retinal degeneration in rats induced by CI-1010, a 2-nitroimidazole radiosensitizer

Toxicologic Pathology
M A BreiderA W Gough

Abstract

The anti-cancer compound CI-1010, designated as (R)-alpha-([(2-bromoethyl)amino]methyl)-2-nitro-1H-imidazole-1-ethanol monohydrobromide, has a proposed dual mechanism of action due to alkylating and radiosensitizing activities. To assess potential toxicity, adult Wistar rats were treated with a single intravenous injection (0, 50, 100, 150, 225, or 350 mg/kg) and necropsied at 4 or 29 days following treatment. In a repeated dose experiment, rats were injected daily (0, 10, 40, or 80 mg/kg; 5 doses/wk) for 3 wk and necropsied at the end of week 3 or 7. CI-1010 induced retinal degeneration by 4 days after a single injection of > or = 225 mg/kg or by 3 wk of repeated injections of > or = 40 mg/kg. The locally extensive to diffuse retinal degeneration involved the photoreceptor and outer nuclear layer. The photoreceptor layer was vacuolated and compressed corresponding to ultrastructural evidence of inner segment swelling and outer segment fragmentation. The outer nuclear layer was thinned due to loss of nuclei and contained numerous pyknotic or karyorrhectic nuclei. These nuclear changes were morphologically consistent with apoptosis and many outer nuclear layer nuclei labeled with in situ TdT-mediated dUTP-digoxigenin nick end la...Continue Reading

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Citations

Oct 16, 2001·European Journal of Medicinal Chemistry·W A Denny
Mar 22, 2002·The Lancet Oncology·W A Denny
Apr 18, 2008·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Natsuho YamamotoTrevor W Hambley
Aug 9, 2008·Medicinal Research Reviews·Yu Chen, Longqin Hu
Feb 9, 2000·Toxicology and Applied Pharmacology·A E Lee, W R Wilson
Nov 14, 2008·Journal of Enzyme Inhibition and Medicinal Chemistry·Dharmarajan SriramPerumal Yogeeswari
Oct 28, 1998·Toxicologic Pathology·M A BreiderA W Gough
Nov 30, 2004·Cancer Investigation·William A Denny
Jan 6, 2011·Basic & Clinical Pharmacology & Toxicology·Maria V PapadopoulouWilliam D Bloomer
Dec 24, 2018·Chemical Society Reviews·Amit SharmaJong Seung Kim
Nov 6, 2015·Journal of Toxicologic Pathology·Kazumoto ShibuyaSeiji Otake
Jul 4, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Adam V PattersonWilliam R Wilson
Dec 21, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jessica D SunCharles P Hart
Apr 3, 2009·Journal of Enzyme Inhibition and Medicinal Chemistry·Peter EbbesenAndrea Scozzafava
Dec 12, 2001·Current Problems in Cancer·M M PoggiJ B Mitchell

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