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Radiosensitizer sanazole (AK-2123) enhances gamma-radiation-induced apoptosis in murine fibrosarcoma.

Abstract
Sanazole (AK-2123) (N-2'-methoxy ethyl)-2-(3"-nitro-1"-triazolyl)acetamide, which has completed phase III clinical trials as a radiosensitizer, enhanced gamma-radiation induced apoptosis in murine fibrosarcoma upon i.p. administration at 40 mg/kg body weight one hour prior to irradiation. A microscopic examination of Giemsa-May-Grunwald stained cells has shown a higher frequency of condensed nuclei and fragmented nuclei in the tumor cells. The administration of sanazole to tumor-bearing animals enhanced the radiation-induced internucleosomal fragmentation in the nuclear genome of tumor cells. Higher levels of caspase-3 activity were also observed in the cell extracts of tumours from AK-2123 administered mice. Exposure to gamma-radiation of AK-2123-treated mouse further enhanced the caspase-3 activity, indicating the induction of apoptosis. The radiation sensitization property of sanazole was discernible by comparing the relative tumor diameter following irradiation after i.p. administration of AK-2123 and irradiation alone; it was higher during the first few days followed by the treatment.
AuthorsRema Rajagopalan, Tsutomu V Kagiya, Cherupally Krishnan Krishnan Nair
JournalJournal of radiation research (J Radiat Res) Vol. 44 Issue 4 Pg. 359-65 (Dec 2003) ISSN: 0449-3060 [Print] Japan
PMID15031563 (Publication Type: Journal Article)
Chemical References
  • Nucleosomes
  • Radiation-Sensitizing Agents
  • Triazoles
  • AK 2123
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases
Topics
  • Animals
  • Apoptosis
  • Caspase 3
  • Caspases (biosynthesis)
  • Cell Nucleus (metabolism)
  • DNA Fragmentation
  • Fibrosarcoma (pathology)
  • Gamma Rays
  • Genome
  • Male
  • Mice
  • Neoplasm Transplantation
  • Neoplasms, Radiation-Induced (pathology)
  • Nucleosomes (metabolism)
  • Radiation-Sensitizing Agents (pharmacology)
  • Sarcoma, Experimental (pathology)
  • Time Factors
  • Triazoles (pharmacology)

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