Differential effect of IP- and IV-injected nitrogen mustard on subsequently-irradiated intestinal crypts: implications for 'dose-effect factors' predicted by experimental, combined modality therapy.
dc.contributor.author | Moore, James V | |
dc.date.accessioned | 2011-03-13T00:10:23Z | |
dc.date.available | 2011-03-13T00:10:23Z | |
dc.date.issued | 1984-05 | |
dc.identifier.citation | Differential effect of IP- and IV-injected nitrogen mustard on subsequently-irradiated intestinal crypts: implications for 'dose-effect factors' predicted by experimental, combined modality therapy. 1984, 57 (677):403-7 Br J Radiol | en |
dc.identifier.issn | 0007-1285 | |
dc.identifier.pmid | 6722435 | |
dc.identifier.doi | 10.1259/0007-1285-57-677-403 | |
dc.identifier.uri | http://hdl.handle.net/10541/124432 | |
dc.description.abstract | In experimental chemotherapy-radiotherapy, cytotoxic drugs are almost invariably injected by the intraperitoneal (IP) route. This contrasts with normal clinical practice, which is to employ the intravenous (IV) route. We have used a clonogenic assay of gastrointestinal (GI) injury in mice to show that a given administered dose of nitrogen mustard (HN2), injected IP, results in a much greater reduction in the subsequent radiation dose required to achieve an isoeffect, than if the drug is injected IV. At an administered dose of 3.5 mg kg-1 of HN2 (the animal LD10/30 for IP injection), the radiation dose-reduction factor for 10% survival of intestinal crypts, was 1.94 for IP HN2 and only 1.28 for IV HN2. Even the grossly-equitoxic (mouse LD10/30) dose of IV HN2 resulted in a smaller predicted radiation dose reduction for GI injury, by a factor of 1.45. The validity of using the IP route in combined chemotherapy-radiotherapy studies designed to generate quantitative estimates of toxicity is discussed. | |
dc.language.iso | en | en |
dc.subject.mesh | Animals | |
dc.subject.mesh | Cell Survival | |
dc.subject.mesh | Clone Cells | |
dc.subject.mesh | Combined Modality Therapy | |
dc.subject.mesh | Dose-Response Relationship, Drug | |
dc.subject.mesh | Dose-Response Relationship, Radiation | |
dc.subject.mesh | Gamma Rays | |
dc.subject.mesh | Injections, Intraperitoneal | |
dc.subject.mesh | Injections, Intravenous | |
dc.subject.mesh | Jejunum | |
dc.subject.mesh | Male | |
dc.subject.mesh | Mechlorethamine | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Mice, Inbred Strains | |
dc.title | Differential effect of IP- and IV-injected nitrogen mustard on subsequently-irradiated intestinal crypts: implications for 'dose-effect factors' predicted by experimental, combined modality therapy. | en |
dc.type | Article | en |
dc.identifier.eissn | 1748-880X | |
dc.contributor.department | Paterson Laboratories, Christie Hospital and Holt Radium Institute, Wilmslow Road, Withington, Manchester M20 9BX, UK | en |
dc.identifier.journal | The British journal of Radiology | en |
html.description.abstract | In experimental chemotherapy-radiotherapy, cytotoxic drugs are almost invariably injected by the intraperitoneal (IP) route. This contrasts with normal clinical practice, which is to employ the intravenous (IV) route. We have used a clonogenic assay of gastrointestinal (GI) injury in mice to show that a given administered dose of nitrogen mustard (HN2), injected IP, results in a much greater reduction in the subsequent radiation dose required to achieve an isoeffect, than if the drug is injected IV. At an administered dose of 3.5 mg kg-1 of HN2 (the animal LD10/30 for IP injection), the radiation dose-reduction factor for 10% survival of intestinal crypts, was 1.94 for IP HN2 and only 1.28 for IV HN2. Even the grossly-equitoxic (mouse LD10/30) dose of IV HN2 resulted in a smaller predicted radiation dose reduction for GI injury, by a factor of 1.45. The validity of using the IP route in combined chemotherapy-radiotherapy studies designed to generate quantitative estimates of toxicity is discussed. |