Biomaterial Database

Altered 5-phosphoribosyl 1-pyrophosphate amidotransferase activity in 6-thioguanine-resistant HL-60 human acute promyelocytic leukemia cells. 1984

K Ishiguro, and A C Sartorelli

A novel mechanism of resistance to the antileukemic agent 6-thioguanine (TGua) was demonstrated in a clone (TGuo-30-2) derived from HL-60 human acute promyelocytic leukemia cells. The clone was isolated by prescreening mutagenized HL-60 cells in hypoxanthine-amethopterin-thymidine medium, followed by selection with 6-thioguanosine. TGuo-30-2 cells were cross-resistant to TGua and beta-2'-deoxythioguanosine. TGuo-30-2 cells exhibited a marked decrease in the capacity to accumulate intracellular TGua nucleotides after treatment with TGua. The decrease in accumulation was not caused by a defect in transport, a lack or alteration of hypoxanthine-guanine phosphoribosyltransferase activity, or enhanced degradation of TGua nucleotides but appeared to be due to the maintenance of a lowered level of 5-phosphoribosyl 1-pyrophosphate (PRPP) in the resistant variant, which corresponded to 20% of the parental concentration. Despite the decrease in PRPP levels, incorporation of glycine into purine nucleotides was greater in TGuo-30-2 than in parental cells. Measurement of PRPP amidotransferase activity using cell homogenates revealed altered kinetics for the enzyme from TGuo-30-2 cells, which included significant loss of sensitivity to feedback inhibition by 6-thioguanosine 5'-phosphate and greater catalytic activity at low concentrations of PRPP.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D010430	Pentosyltransferases	Enzymes of the transferase class that catalyze the transfer of a pentose group from one compound to another.
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
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
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000582	Amidophosphoribosyltransferase	An enzyme, involved in the early steps of purine nucleotide biosynthesis, that catalyzes the formation of 5-phosphoribosylamine from glutamine and phosphoribosylpyrophosphate. EC 2.4.2.14.	Glutamine Phosphoribosyl Pyrophosphate Amidotransferase,Phosphoribosyl Pyrophosphate Amidotransferase,Glutamine-Amidophosphoribosyltransferase,Phosphoribosyldiphosphate 5-Amidotransferase,5-Amidotransferase, Phosphoribosyldiphosphate,Amidotransferase, Phosphoribosyl Pyrophosphate,Glutamine Amidophosphoribosyltransferase,Phosphoribosyldiphosphate 5 Amidotransferase,Pyrophosphate Amidotransferase, Phosphoribosyl
D001692	Biological Transport	The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.	Transport, Biological,Biologic Transport,Transport, Biologic
D001711	Biotransformation	The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
D013866	Thioguanine	An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia.	6-Thioguanine,2-Amino-6-Purinethiol,Lanvis,Tabloid,Thioguanin-GSK,Thioguanine Anhydrous,Thioguanine Hemihydrate,Thioguanine Monosodium Salt,Thioguanine Tabloid,Tioguanina Wellcome,Tioguanine,2 Amino 6 Purinethiol,6 Thioguanine,Anhydrous, Thioguanine,Thioguanin GSK,ThioguaninGSK
D015470	Leukemia, Myeloid, Acute	Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.	Leukemia, Myelogenous, Acute,Leukemia, Nonlymphocytic, Acute,Myeloid Leukemia, Acute,Nonlymphocytic Leukemia, Acute,ANLL,Acute Myelogenous Leukemia,Acute Myeloid Leukemia,Acute Myeloid Leukemia with Maturation,Acute Myeloid Leukemia without Maturation,Leukemia, Acute Myelogenous,Leukemia, Acute Myeloid,Leukemia, Myeloblastic, Acute,Leukemia, Myelocytic, Acute,Leukemia, Myeloid, Acute, M1,Leukemia, Myeloid, Acute, M2,Leukemia, Nonlymphoblastic, Acute,Myeloblastic Leukemia, Acute,Myelocytic Leukemia, Acute,Myelogenous Leukemia, Acute,Myeloid Leukemia, Acute, M1,Myeloid Leukemia, Acute, M2,Nonlymphoblastic Leukemia, Acute,Acute Myeloblastic Leukemia,Acute Myeloblastic Leukemias,Acute Myelocytic Leukemia,Acute Myelocytic Leukemias,Acute Myelogenous Leukemias,Acute Myeloid Leukemias,Acute Nonlymphoblastic Leukemia,Acute Nonlymphoblastic Leukemias,Acute Nonlymphocytic Leukemia,Acute Nonlymphocytic Leukemias,Leukemia, Acute Myeloblastic,Leukemia, Acute Myelocytic,Leukemia, Acute Nonlymphoblastic,Leukemia, Acute Nonlymphocytic,Leukemias, Acute Myeloblastic,Leukemias, Acute Myelocytic,Leukemias, Acute Myelogenous,Leukemias, Acute Myeloid,Leukemias, Acute Nonlymphoblastic,Leukemias, Acute Nonlymphocytic,Myeloblastic Leukemias, Acute,Myelocytic Leukemias, Acute,Myelogenous Leukemias, Acute,Myeloid Leukemias, Acute,Nonlymphoblastic Leukemias, Acute,Nonlymphocytic Leukemias, Acute