Biomaterial Database

Combination effects of cis-dichlorodiammineplatinum with selected metahalones, pyrimidine sulfoxides and pyrimidine sulfones on human NHIK 3025 cells in vitro. 1988

J M Dornish, and K Undheim, and E O Pettersen, and R Oftebro, and S G Laland

Department of Tissue Culture, Norwegian Radium Hospital, Oslo.

Synergistic cell inactivating effects were displayed when human NHIK 3025 cells cultivated in vitro were treated with cis-dichlorodiammineplatinum(II) (cis-DDP) in simultaneous combination with selected metahalones, pyrimidine sulfoxides and sulfones. Cell inactivation was measured as the percentage of single cells surviving and able to give rise to macroscopic colonies following drug treatment. Selection of compounds was made according to the presence and position of certain structural groups. For 5-halo-pyrimidin-2-ones (the metahalones), a propargyl substituent attached to the pyrimidine ring at the 1-position resulted in compounds causing potentiation of cis-DDP-induced cell inactivation. An iodo or trifluoromethyl substituent at the 5-position led to a reduction in cis-DDP + metahalone synergism respective to a 5-chloro substituent. Cell survival following 1 h treatment with the metahalones alone was always near 100%. The cell inactivating effect of pyrimidine sulfoxides and sulfones alone and in simultaneous combination with cis-DDP was also investigated. Treatment of human cells with pyrimidine sulfoxides and sulfones alone resulted in reduced cell survival relative to the metahalones. When tested in combination with cis-DDP, pyrimidine sulfoxides and sulfones containing a propargyl moiety bound at the sulfur atom were found to potentiate the cell inactivating effect of cis-DDP. Other substituents induced only minor effects.

UI	MeSH Term	Description	Entries
D011743	Pyrimidines	A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D011744	Pyrimidinones	Heterocyclic compounds known as 2-pyrimidones (or 2-hydroxypyrimidines) and 4-pyrimidones (or 4-hydroxypyrimidines) with the general formula C4H4N2O.	Pyrimidinone,Pyrimidone,Pyrimidones
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
D002945	Cisplatin	An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.	Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
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
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013450	Sulfones		Sulfone
D013454	Sulfoxides	Organic compounds that have the general formula R-SO-R. They are obtained by oxidation of mercaptans (analogous to the ketones). (From Hackh's Chemical Dictionary, 4th ed)
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured