The modification of melphalan toxicity in tumor bearing mice by s-2-(3-aminopropylamino)- ethylphosphorothioic acid (WR 2721)
Journal Article
·
· Am. J. Clin. Oncol.; (United States)
The toxicity of melphalan in mice was reduced by the injection of S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR2721). This was seen in terms of reduced toxicity to the stem cells of the bone marrow and intestinal epithelium as well as improved animal survival. Using human melanoma xenografts and growth delay as an end-point, it was demonstrated that WR2721 did not protect this tumor from melphalan. With radio-labelled WR2721, it was shown that WR2721 was rapidly cleared from the blood and actively accumulated by all normal tissues except the CNS. Intact human tumor xenografts and Lewis lung tumors were less able to accumulate WR2721 than normal tissues, but in vitro studies showed that tissue fragments or single cell suspensions of tumors were as efficient as liver fragments or bone marrow cells in accumulating the drug. The rapid clearance of WR2721 and poor vascularity of the intact tumors were thought to be responsible for the differential uptake and protection of normal tissues by WR2721.
- Research Organization:
- Division of Physics, Institute of Cancer Research, Sutton, Surrey, England
- OSTI ID:
- 6702425
- Journal Information:
- Am. J. Clin. Oncol.; (United States), Journal Name: Am. J. Clin. Oncol.; (United States) Vol. 5:3; ISSN AJCOD
- Country of Publication:
- United States
- Language:
- English
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560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATING AGENTS
AMINES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL EFFECTS
BODY
BONE MARROW
CLEARANCE
DISEASES
EPITHELIUM
ESTERS
HEMATOPOIETIC SYSTEM
LABELLED COMPOUNDS
LUNGS
MAMMALS
MICE
NEOPLASMS
NITROGEN MUSTARD
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PHARMACOLOGY
PHOSPHORIC ACID ESTERS
RESPIRATORY SYSTEM
RODENTS
SOMATIC CELLS
STEM CELLS
TISSUES
TOXICITY
TUMOR CELLS
VERTEBRATES
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATING AGENTS
AMINES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL EFFECTS
BODY
BONE MARROW
CLEARANCE
DISEASES
EPITHELIUM
ESTERS
HEMATOPOIETIC SYSTEM
LABELLED COMPOUNDS
LUNGS
MAMMALS
MICE
NEOPLASMS
NITROGEN MUSTARD
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PHARMACOLOGY
PHOSPHORIC ACID ESTERS
RESPIRATORY SYSTEM
RODENTS
SOMATIC CELLS
STEM CELLS
TISSUES
TOXICITY
TUMOR CELLS
VERTEBRATES