BIOMAT Database Logo BIOMAT Database Logo

Effect of partition coefficient on the ability of nitroimidazoles to enhance the cytotoxicity of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. 1983

D G Hirst, and J M Brown, and J L Hazlehurst

The ability of three nitroimidazoles [SR-2508, misonidazole (MISO), and benznidazole] with differing octanol-water partition coefficients to enhance the cytotoxicity of the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was evaluated in two mouse tumors (the KHT sarcoma and the SCC VII/St carcinoma). These results were compared with the effect on two normal tissues (bone marrow CFU-S and testis spermatogonia). When given as a large single dose, benznidazole was more effective than MISO in enhancing the cytotoxicity of CCNU to both tumors. SR-2508 had no effect. The advantage of benznidazole over MISO was lost, however, because benznidazole gave more toxicity in the normal tissues than MISO. In experiments where the nitroimidazoles were administered by multiple small injections to maintain a blood plasma level between 50 and 100 micrograms/ml, benznidazole was also more effective than MISO in enhancing CCNU cytotoxicity in the tumors. In each case, enhancement was rather less than that obtained with large single injections. Again, however, benznidazole did not produce a consistently greater therapeutic gain than MISO because it also enhanced normal tissue toxicity while MISO did not. SR-2508 was ineffective in both tumors and normal tissues. We conclude that neither SR-2508 nor benznidazole are superior to MISO in combination with CCNU.

UI MeSH Term Description Entries
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D008130 Lomustine An alkylating agent of value against both hematologic malignancies and solid tumors. CCNU,Belustine,Cecenu,CeeNU,NSC-79037,NSC 79037,NSC79037
D008297 Male Males
D008809 Mice, Inbred C3H An inbred strain of mouse that is used as a general purpose strain in a wide variety of RESEARCH areas including CANCER; INFECTIOUS DISEASES; sensorineural, and cardiovascular biology research. Mice, C3H,Mouse, C3H,Mouse, Inbred C3H,C3H Mice,C3H Mice, Inbred,C3H Mouse,C3H Mouse, Inbred,Inbred C3H Mice,Inbred C3H Mouse
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D009593 Nitroimidazoles IMIDAZOLES having a nitro moiety. Nitroimidazole
D009607 Nitrosourea Compounds A class of compounds in which the core molecule is R-NO, where R is UREA. Compounds, Nitrosourea
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
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
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug

Related Publications

D G Hirst, and J M Brown, and J L Hazlehurst
1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea.
January 2004, Report on carcinogens : carcinogen profiles,
D G Hirst, and J M Brown, and J L Hazlehurst
1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea.
January 2002, Report on carcinogens : carcinogen profiles,
D G Hirst, and J M Brown, and J L Hazlehurst
Nitrosourea chemotherapeutic agents: 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea.
January 2011, Report on carcinogens : carcinogen profiles,
D G Hirst, and J M Brown, and J L Hazlehurst
1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU).
May 1981, IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans,
D G Hirst, and J M Brown, and J L Hazlehurst
Hydroxylation of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.
December 1975, Biochemical pharmacology,
D G Hirst, and J M Brown, and J L Hazlehurst
Effect of phospholipids on maintenance of the cytotoxicity of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in aqueous suspension.
May 1978, Journal of the National Cancer Institute,
D G Hirst, and J M Brown, and J L Hazlehurst
Urinary metabolites of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea.
January 1981, Drug metabolism and disposition: the biological fate of chemicals,
D G Hirst, and J M Brown, and J L Hazlehurst
Physiologic disposition of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea (Me CCNU) in man.
May 1973, Cancer,
D G Hirst, and J M Brown, and J L Hazlehurst
Reactions of 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea in aqueous solution.
October 1979, Journal of medicinal chemistry,
D G Hirst, and J M Brown, and J L Hazlehurst
Clinical studies with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (NSC 79037).
March 1971, Cancer research,
Copied contents to your clipboard!