Factors influencing the chemosensitization of melphalan by misonidazole. 1985

V S Randhawa, and F A Stewart, and J Denekamp, and M R Stratford

The effect of melphalan alone or combined with various schedules of misonidazole (MISO) has been tested on a murine fibrosarcoma. The tumoricidal effect has been determined using the growth delay assay. Large single doses (500-1000 mgkg-1) of MISO enhanced the anti-tumour effect of melphalan, especially at high melphalan doses. This was accompanied by a drop in body and tumour temperature and an increase in the melphalan half-life. The MISO-induced hypothermia was prevented in one experiment by keeping the mice in an ambient temperature of 35 degrees C for 3 h. This reduced the exposure to melphalan but did not diminish the cytotoxic effect of the drug combination. Chronic administration of MISO for an 8 h period gave no enhancement of melphalan damage, whether melphalan was given half-way through or at the end of the period of dosing. It seems that a threshold tumour concentration of MISO, in excess of 70 micrograms g-1, is needed for enhancement of melphalan cytotoxicity; prolonged exposures to very low doses are ineffective.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008558 Melphalan An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen. Medphalan,Merphalan,Phenylalanine Mustard,Sarcolysine,Sarkolysin,4-(Bis(2-chloroethyl)amino)phenylalanine,Alkeran,L-PAM,Mustard, Phenylalanine
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D008920 Misonidazole A nitroimidazole that sensitizes normally radio-resistant hypoxic cells to radiation. It may also be directly cytotoxic to hypoxic cells and has been proposed as an antineoplastic. Ro 07-0582,Ro 7-0582,alpha-(Methoxymethyl)-2-nitro-1H-imidazole-1-ethanol,Ro 07 0582,Ro 070582,Ro 7 0582,Ro 70582
D009593 Nitroimidazoles IMIDAZOLES having a nitro moiety. Nitroimidazole
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
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
D005354 Fibrosarcoma A sarcoma derived from deep fibrous tissue, characterized by bundles of immature proliferating fibroblasts with variable collagen formation, which tends to invade locally and metastasize by the bloodstream. (Stedman, 25th ed) Fibrosarcomas
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013696 Temperature The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms. Temperatures

Related Publications

V S Randhawa, and F A Stewart, and J Denekamp, and M R Stratford
May 1989, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology,
V S Randhawa, and F A Stewart, and J Denekamp, and M R Stratford
January 1982, International journal of radiation oncology, biology, physics,
V S Randhawa, and F A Stewart, and J Denekamp, and M R Stratford
December 1986, British journal of cancer,
V S Randhawa, and F A Stewart, and J Denekamp, and M R Stratford
January 1982, International journal of radiation oncology, biology, physics,
V S Randhawa, and F A Stewart, and J Denekamp, and M R Stratford
January 1992, International journal of radiation oncology, biology, physics,
V S Randhawa, and F A Stewart, and J Denekamp, and M R Stratford
September 1986, Cancer treatment reports,
V S Randhawa, and F A Stewart, and J Denekamp, and M R Stratford
August 1987, British journal of cancer,
V S Randhawa, and F A Stewart, and J Denekamp, and M R Stratford
January 1982, International journal of radiation oncology, biology, physics,
V S Randhawa, and F A Stewart, and J Denekamp, and M R Stratford
September 1984, International journal of radiation oncology, biology, physics,
V S Randhawa, and F A Stewart, and J Denekamp, and M R Stratford
April 1988, Journal of clinical oncology : official journal of the American Society of Clinical Oncology,
Copied contents to your clipboard!