Sensitivity of human and murine hematopoietic precursor cells to 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose and 1,3-bis(2-chloroethyl)-1-nitrosourea. 1978

P S Schein, and J M Bull, and D Doukas, and D Hoth

The sensitivity of mouse and human bone marrow hematopoietic precursor cells [colony-forming units committed to granulocyte-macrophage differentiatin (CFU-C)] was determined after in vitro incubation with chlorozotocin (2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose), or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), with the use of drug concentrations achieved during clinical administration. Chlorozotocin, at a concentration of 1 X 10(-4) M, did not decrease mouse CFU-C below the control of 44 colonies/10(5) nucleated cells; 5 X 10(-4) M produced a 70% reduction in CFU-C, and 1 X 10(-3) M chlorozotocin eliminated all colony formation. In contrast, BCNU at 1 X 10(-4) M resulted in a 55% reduction in CFU-C, and at 5 X 10(-4) M it eliminated all colony formation. For human marrow the threshold concentration for chlorozotocin toxicity was 1 X 10(4) M, which resulted in 25% reduction in CFU-C as compared to the control of 32 colonies/10(5) nucleated cells. In contrast, BCNU at 5 X 10(-5) M decreased human CFU-C to 47% of control, and at 1 X 10(-4) M it eliminated all colony formation. Twenty-four hr after in vitro exposure to 1 X 10(-4) M chlorozotocin, there was no reduction in human bone marrow DNA synthesis in contrast to a 42% reduction with 1 X 10(-4) M BCNU. The plasma concentration of drugs following a therapeutic dose in patients was measured and was found to correspond to the concentration range used in the in vitro studies of marrow toxicity.

UI MeSH Term Description Entries
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008722 Methods A series of steps taken in order to conduct research. Techniques,Methodological Studies,Methodological Study,Procedures,Studies, Methodological,Study, Methodological,Method,Procedure,Technique
D009607 Nitrosourea Compounds A class of compounds in which the core molecule is R-NO, where R is UREA. Compounds, Nitrosourea
D002330 Carmustine A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed) BCNU,1,3-Bis(2-Chloroethyl)-1-Nitrosourea,BiCNU,FIVB,N,N'-Bis(2-Chloroethyl)-N-Nitrosourea,Nitrumon
D002452 Cell Count The number of CELLS of a specific kind, usually measured per unit volume or area of sample. Cell Density,Cell Number,Cell Counts,Cell Densities,Cell Numbers,Count, Cell,Counts, Cell,Densities, Cell,Density, Cell,Number, Cell,Numbers, Cell
D002999 Clone Cells A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed) Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006098 Granulocytes Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the NEUTROPHILS; EOSINOPHILS; and BASOPHILS. Granulocyte
D006412 Hematopoietic Stem Cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Colony-Forming Units, Hematopoietic,Progenitor Cells, Hematopoietic,Stem Cells, Hematopoietic,Hematopoietic Progenitor Cells,Cell, Hematopoietic Progenitor,Cell, Hematopoietic Stem,Cells, Hematopoietic Progenitor,Cells, Hematopoietic Stem,Colony Forming Units, Hematopoietic,Colony-Forming Unit, Hematopoietic,Hematopoietic Colony-Forming Unit,Hematopoietic Colony-Forming Units,Hematopoietic Progenitor Cell,Hematopoietic Stem Cell,Progenitor Cell, Hematopoietic,Stem Cell, Hematopoietic,Unit, Hematopoietic Colony-Forming,Units, Hematopoietic Colony-Forming

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