Biomaterial Database

Selective reduction of intracellular guanosine 5'-triphosphate pool by 4-carbamoylimidazolium 5-olate in murine tumor cells. 1986

M Fukui, and M Inaba, and S Tsukagoshi, and Y Sakurai

Ehrlich carcinoma and P388 leukemia cells were rendered resistant to 4-carbamoylimidazolium 5-olate (SM-108), and assessments were made of biochemical and pharmacological determinants for the sensitivity to SM-108 using both sensitive and resistant sublines. We observed that the treatment of cells with SM-108 in vitro caused a remarkable decrease in the intracellular guanosine 5'-triphosphate pool level in sensitive but not in resistant sublines. There was no difference in the ability to take up SM-108 between sensitive and resistant sublines, but the cellular conversion of SM-108 to its nucleotide, which is the putative active anabolite of SM-108, proceeded only in sensitive sublines. Enzymological studies revealed that the activity of adenine phosphoribosyltransferase (EC 2.4.2.7), which is believed to conjugate SM-108 with 5-phospho-alpha-D-ribose 1-diphosphate, was very low in the resistant sublines. These results strongly support our previous hypothesis that SM-108 is activated by adenine phosphoribosyltransferase to SM-108-nucleotide which then inhibits hypoxanthine-5'-monophosphate dehydrogenase (EC 1.2.1.14), a key enzyme for the de novo synthesis of guanosine 5'-monophosphate.

UI	MeSH Term	Description	Entries
D007093	Imidazoles	Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D007168	IMP Dehydrogenase	An enzyme that catalyzes the dehydrogenation of inosine 5'-phosphate to xanthosine 5'-phosphate in the presence of NAD. EC 1.1.1.205.	Inosinic Acid Dehydrogenase,Inosine-5-Monophosphate Dehydrogenase,Acid Dehydrogenase, Inosinic,Dehydrogenase, IMP,Dehydrogenase, Inosine-5-Monophosphate,Dehydrogenase, Inosinic Acid,Inosine 5 Monophosphate Dehydrogenase
D007941	Leukemia P388	An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.	P388D(1) Leukemia,P388, Leukemia
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
D002286	Carcinoma, Ehrlich Tumor	A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.	Ehrlich Ascites Tumor,Ascites Tumor, Ehrlich,Ehrlich Tumor Carcinoma,Tumor, Ehrlich Ascites
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D004351	Drug Resistance	Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.	Resistance, Drug
D006160	Guanosine Triphosphate	Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.	GTP,Triphosphate, Guanosine
D000228	Adenine Phosphoribosyltransferase	An enzyme catalyzing the formation of AMP from adenine and phosphoribosylpyrophosphate. It can act as a salvage enzyme for recycling of adenine into nucleic acids. EC 2.4.2.7.	AMP Pyrophosphorylase,Transphosphoribosidase,APRTase,Phosphoribosyltransferase, Adenine,Pyrophosphorylase, AMP
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