Effects of single and combined chemotherapeutic agents on hemopoietic stem cells in mice. 1976

V K Jenkins, and J J Costanzi, and H N Ellis

Bone marrow cell responses to injections of nitrogen mustard, oncovin, procarbazine, hydrocortisone, and a regimen of all four drugs (MOPH) were evaluated in CRF1 and C57B1/6 mice by determining bone marrow cellularity and content of transplantable colony forming units (CFU) after treatment. The study was done to determine whether the combined regimen, which is widely used clinically in treatment of disseminated Hodgkin's disease, is more or less detrimental to the hemopoietic system than the same drugs used as single agents. Nitrogen mustard and procarbazine used clinically as single drugs are given in three and two times, respectively, greater doses than in the combined regimen. Hydrocortisone, given singly, was least toxic of the drugs, reducing the CFU/femur to 63% and 71% of control values. MOPH appeared slightly more toxic than hydrocortisone, resulting in 41% and 52% of the CFU/femur surviving, and was about equally as toxic as oncovin alone. Nitrogen mustard and procarbazine, administered as single drugs in high doses, were highly suppressive, resulting in only 10-19% survival of CFU/femur, whereas, reduced doses of the two drugs as used in the MOPH regimen spared 30-45% of the CFU/femur. Survival of CFU after MOPH treatment was three to four times greater than after high doses of nitrogen mustard or procarbazine alone. The component drugs of the combined regimen did not act on separate populations of stem cells to produce an additive effect but appeared to inactivate the same population of cells.

UI MeSH Term Description Entries
D008297 Male Males
D008466 Mechlorethamine A biologic alkylating agent that exerts its cytotoxic effects by forming DNA ADDUCTS and DNA interstrand crosslinks, thereby inhibiting rapidly proliferating cells. The hydrochloride is an antineoplastic agent used to treat HODGKIN DISEASE and LYMPHOMA. Chlorethazine,Chlormethine,Mechlorethamine Oxide,Mustine,Nitrogen Mustard,Nitrogen Mustard N-Oxide,Bis(2-chloroethyl)methylamine,Caryolysine,Cloramin,Embichin,Mechlorethamine Hydrochloride,Mechlorethamine Hydrochloride N-Oxide,Mechlorethamine N-Oxide,Methylchlorethamine,Mitomen,Mustargen,NSC-10107,NSC-762,Nitrogranulogen,Nitromin,Hydrochloride N-Oxide, Mechlorethamine,Hydrochloride, Mechlorethamine,Mechlorethamine Hydrochloride N Oxide,Mechlorethamine N Oxide,N-Oxide, Mechlorethamine Hydrochloride,N-Oxide, Nitrogen Mustard,NSC 10107,NSC 762,NSC10107,NSC762,Nitrogen Mustard N Oxide
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D011344 Procarbazine An antineoplastic agent used primarily in combination with mechlorethamine, vincristine, and prednisone (the MOPP protocol) in the treatment of Hodgkin's disease. Matulane,Natulan,Procarbazine Hydrochloride,Procarbazine Monohydrobromide,Procarbazine Monohydrochloride,Hydrochloride, Procarbazine,Monohydrobromide, Procarbazine,Monohydrochloride, Procarbazine
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
D004353 Drug Evaluation, Preclinical Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D004359 Drug Therapy, Combination Therapy with two or more separate preparations given for a combined effect. Combination Chemotherapy,Polychemotherapy,Chemotherapy, Combination,Combination Drug Therapy,Drug Polytherapy,Therapy, Combination Drug,Chemotherapies, Combination,Combination Chemotherapies,Combination Drug Therapies,Drug Polytherapies,Drug Therapies, Combination,Polychemotherapies,Polytherapies, Drug,Polytherapy, Drug,Therapies, Combination Drug
D005260 Female Females
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
D006854 Hydrocortisone The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. Cortef,Cortisol,Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-,11-Epicortisol,Cortifair,Cortril,Epicortisol,Hydrocortisone, (11 alpha)-Isomer,Hydrocortisone, (9 beta,10 alpha,11 alpha)-Isomer,11 Epicortisol

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