title: 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.
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, India. cknair@magnum.barc.ernet.in
authors.forename: Rema
authors.initials: R
authors.lastname: Rajagopalan
authors.forename: Tsutomu V
authors.initials: TV
authors.lastname: Kagiya
authors.forename: Cherupally Krishnan Krishnan
authors.initials: CK
authors.lastname: Nair
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D002467:Cell Nucleus / Q000378:metabolism; D053938:DNA Fragmentation; D005354:Fibrosarcoma / Q000473:pathology*; D005720:Gamma Rays; D016678:Genome; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009381:Neoplasms, Radiation-Induced / Q000473:pathology; D009707:Nucleosomes / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012513:Sarcoma, Experimental / Q000473:pathology; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D009707:Nucleosomes; D011838:Radiation-Sensitizing Agents; D014230:Triazoles; C072690:AK 2123; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases