Biomaterial Database

Potentiation of nitrogen mustard cytotoxicity by disulfiram, diethyldithiocarbamic acid, and diethylamine in mice. 1989

F Valeriote, and H E Grates

Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201.

Disulfiram (DSF) and its metabolites, diethyldithiocarbamic acid (DDC) and diethylamine (DEA), were studied as pretreatments in combination with the alkylating agent nitrogen mustard (HN2) on the cytotoxicity of HN2 against both leukemia cells and normal hematopoietic stem cells. Both time intervals and dose relationships were examined. DSF showed a substantial potentiation of HN2 cytotoxicity against murine AKR leukemia cell spleen colony-forming units (LCFU) when given i.p. between 15 to 30 min prior to HN2 i.v. treatment. For 3 mg DSF/mouse pretreatment, leukemia LCFU survival was about 10(-6) whereas it was about 10(-2) for HN2 alone. The extent of this potentiation decreased as the time between treatments increased. Significant potentiation was noted even when a low dose of DSF (0.25 mg/mouse) was administered 15 min before HN2. However, DSF had little if any effect on the modulation of HN2 cytotoxicity to normal hematopoietic cell spleen colony-forming units (NCFU). DDC showed an increasing potentiation of HN2 cytotoxicity against LCFU when given i.p. prior to HN2 i.v. treatment. The maximum effect was noted between 2 and 4 h with a surviving fraction for LCFU between 10(-5) and 10(-6) for 20 mg/mouse DDC pretreatment. The extent of this effect then decreased as the time interval increased beyond 4 h, but it was still significant for the 24-h interval. This pronounced potentiation effect was dose dependent for DDC. The compound exhibited a protective effect against HN2 cytotoxicity to NCFU when given 15 min before HN2. This protection decreased with increased time interval. DEA (20 mg/mouse) did not show a significant potentiation of HN2 cytotoxicity against LCFU when administered i.p. prior to HN2. Also, DEA did not show any significant protection of NCFU.

UI	MeSH Term	Description	Entries
D007942	Leukemia, Experimental	Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues.	Experimental Leukemia,Experimental Leukemias,Leukemia Model, Animal,Leukemias, Experimental,Animal Leukemia Model,Animal Leukemia Models,Leukemia Models, Animal
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
D004048	Diethylamines	Diethylamine with the formula CH3CH2NHCH2CH3 and its derivatives.
D004050	Ditiocarb	A chelating agent that has been used to mobilize toxic metals from the tissues of humans and experimental animals. It is the main metabolite of DISULFIRAM.	Diethyldithiocarbamate,Diethylcarbamodithioic Acid,Diethyldithiocarbamic Acid,Dithiocarb,Ditiocarb Sodium,Ditiocarb, Ammonium Salt,Ditiocarb, Bismuth Salt,Ditiocarb, Lead Salt,Ditiocarb, Potassium Salt,Ditiocarb, Sodium Salt,Ditiocarb, Sodium Salt, Trihydrate,Ditiocarb, Tin(4+) Salt,Ditiocarb, Zinc Salt,Imuthiol,Sodium Diethyldithiocarbamate,Thiocarb,Zinc Diethyldithiocarbamate,Ammonium Salt Ditiocarb,Bismuth Salt Ditiocarb,Diethyldithiocarbamate, Sodium,Diethyldithiocarbamate, Zinc,Lead Salt Ditiocarb,Potassium Salt Ditiocarb,Sodium Salt Ditiocarb,Sodium, Ditiocarb,Zinc Salt Ditiocarb
D004221	Disulfiram	A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase.	Tetraethylthiuram Disulfide,Alcophobin,Antabus,Antabuse,Anticol,Bis(diethylthiocarbamoyl) Disulfide,Dicupral,Esperal,Tetraethylthioperoxydicarbonic Diamide, ((H2N)C(S))2S2,Teturam,Disulfide, Tetraethylthiuram
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
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
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
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus