Biomaterial Database

WR-2721 protection of pneumonitis and fibrosis in mouse lung after single doses of x rays. 1984

E L Travis, and C S Parkins, and S J Holmes, and J D Down, and J F Fowler

The radioprotective effect of WR-2721 has been studied in mouse lung after single doses of radiation. Using the breathing rate assay and lethality, radioprotection was assessed at monthly intervals between 3 and 18 months after irradiation during both pneumonitis and chronic fibrosis. The degree of radioprotection was greater for fibrosis than for pneumonitis using both assays. In replicate experiments, dose modifying factors (DMF's) ranging from 1.2 to 1.4 were obtained for pneumonitis and 1.5 and 1.6 for fibrosis. The differences in DMF's for the two phases of lung damage were significant. A difference in the time course of expression of damage was seen in both the breathing rate and lethality assays between mice irradiated with and without WR-2721: the damage ended sooner in the drug-treated mice. This difference is best explained by protection of all damage after 5 months by WR-2721. No evidence of drug toxicity was found. We conclude that WR-2721 protects against chronic lung fibrosis caused by radiation at least as well as against the earlier appearing pneumonitis after single doses of radiation. Thus, if WR-2721 is dose modifying and if late tissue complications are dose limiting in clinical radiotherapy, then a therapeutic benefit would be obtained by the use of this drug in clinical radiotherapy, provided that the radioprotection of tumors did not exceed a factor of 1.5-1.6.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008808	Mice, Inbred CBA	An inbred strain of mouse that is widely used in BIOMEDICAL RESEARCH.	Mice, CBA,Mouse, CBA,Mouse, Inbred CBA,CBA Mice,CBA Mice, Inbred,CBA Mouse,CBA Mouse, Inbred,Inbred CBA Mice,Inbred CBA Mouse
D009946	Organothiophosphorus Compounds	Compounds containing carbon-phosphorus bonds in which the phosphorus component is also bonded to one or more sulfur atoms. Many of these compounds function as CHOLINERGIC AGENTS and as INSECTICIDES.	Compounds, Organothiophosphorus
D011014	Pneumonia	Infection of the lung often accompanied by inflammation.	Experimental Lung Inflammation,Lobar Pneumonia,Lung Inflammation,Pneumonia, Lobar,Pneumonitis,Pulmonary Inflammation,Experimental Lung Inflammations,Inflammation, Experimental Lung,Inflammation, Lung,Inflammation, Pulmonary,Inflammations, Lung,Inflammations, Pulmonary,Lobar Pneumonias,Lung Inflammation, Experimental,Lung Inflammations,Lung Inflammations, Experimental,Pneumonias,Pneumonias, Lobar,Pneumonitides,Pulmonary Inflammations
D011658	Pulmonary Fibrosis	A process in which normal lung tissues are progressively replaced by FIBROBLASTS and COLLAGEN causing an irreversible loss of the ability to transfer oxygen into the bloodstream via PULMONARY ALVEOLI. Patients show progressive DYSPNEA finally resulting in death.	Alveolitis, Fibrosing,Idiopathic Diffuse Interstitial Pulmonary Fibrosis,Fibroses, Pulmonary,Fibrosis, Pulmonary,Pulmonary Fibroses,Alveolitides, Fibrosing,Fibrosing Alveolitides,Fibrosing Alveolitis
D011829	Radiation Dosage	The amount of radiation energy that is deposited in a unit mass of material, such as tissues of plants or animal. In RADIOTHERAPY, radiation dosage is expressed in gray units (Gy). In RADIOLOGIC HEALTH, the dosage is expressed by the product of absorbed dose (Gy) and quality factor (a function of linear energy transfer), and is called radiation dose equivalent in sievert units (Sv).	Sievert Units,Dosage, Radiation,Gray Units,Gy Radiation,Sv Radiation Dose Equivalent,Dosages, Radiation,Radiation Dosages,Units, Gray,Units, Sievert
D011833	Radiation Injuries, Experimental	Experimentally produced harmful effects of ionizing or non-ionizing RADIATION in CHORDATA animals.	Experimental Radiation Injuries,Injuries, Experimental Radiation,Experimental Radiation Injury,Radiation Injury, Experimental
D012129	Respiratory Function Tests	Measurement of the various processes involved in the act of respiration: inspiration, expiration, oxygen and carbon dioxide exchange, lung volume and compliance, etc.	Lung Function Tests,Pulmonary Function Tests,Function Test, Pulmonary,Function Tests, Pulmonary,Pulmonary Function Test,Test, Pulmonary Function,Tests, Pulmonary Function,Function Test, Lung,Function Test, Respiratory,Function Tests, Lung,Function Tests, Respiratory,Lung Function Test,Respiratory Function Test,Test, Lung Function,Test, Respiratory Function,Tests, Lung Function,Tests, Respiratory Function
D004307	Dose-Response Relationship, Radiation	The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation.	Dose Response Relationship, Radiation,Dose-Response Relationships, Radiation,Radiation Dose-Response Relationship,Radiation Dose-Response Relationships,Relationship, Radiation Dose-Response,Relationships, Radiation Dose-Response
D004999	Amifostine	A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia.	Ethiofos,Gammaphos,APAETP,Amifostine Anhydrous,Amifostine Disodium Salt,Amifostine Monohydrate,Amifostine Monohydrochloride,Amifostine Trihydrate,Aminopropyl Aminoethylthiophosphate,Aminopropylaminoethylthiophosphate,Aminopropylaminoethylthiophosphoric Acid,Ethanethiol, 2-((3-aminopropyl)amino)-, dihydrogen phosphate (ester), trihydrate,Ethiofos Anhydrous,Ethyol,NSC-296961,S-(N-(3-Aminopropyl)-2-aminoethyl)thiophosphoric Acid,WR-2721,YM-08310,NSC 296961,NSC296961,WR 2721,WR2721,YM 08310,YM08310