6-Thioguanine (isG) has been used for the past thirty years as an anti-cancer agent in maintenance chemotherapy for childhood acute lymphoblastic leukemia as well as acute myeloid leukemia. Despite its long-standing clinical use, little is understood of the molecular basis of the cytotoxicity associated with 6SG. Research has shown that 6SG is incorporated into DNA during replication after whic...

Flap endonucleases (FENs) are proposed to select their target phosphate diester by unpairing the two terminal nucleotides of duplex. Interstrand disulfide crosslinks, introduced by oxidation of thiouracil and thioguanine bases, abolished the specificity of human FEN1 for hydrolysis one nucleotide into the 5'-duplex.

BACKGROUND Patients with acute lymphoblastic leukemia are often treated with 6-mercaptopurine, and those with homozygous deficiency in thiopurine S-methyltransferase (TPMT) enzyme activity have an extreme sensitivity to this drug as a result of the accumulation of higher cellular concentrations of thioguanine nucleotides. We studied the metabolism, dose requirements, and tolerance of 6-mercapto...

An, J. and A. W. Hsie (1993). "Polymerase chain reaction-based deletion screening of bleomycin induced 6-thioguanine-resistant mutants in Chinese hamster ovary cells: The effects of an inhibitor and a mimic of superoxide dismutase." Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 289(2): 215. http://www.sciencedirect.com/science/article/B6T2C-47PCN7M41/2/3157a48d39359d02b0...

A preliminary report is given of a trial of the T.R.A.P. regimen (thioguanine, rubidomycin, cytosine arabinoside, and prednisolone) for the treatment of acute myeloid leukaemia. Out of 27 patients treated 13 (48.1%) obtained complete remission. The treatment was well tolerated and produced especially good results in elderly patients.

SUMMARY Mice treated simultaneously with 1-0-D-arabinofuranosyl-cytosine (ara-C) and 6-thioguanine (6-TG) were protected from the lethal effects of 6-TG. No protection was afforded if ara-C was given 16 hr before the 6-TG. DNA synthesis in mouse bone marrow was immediately depressed to 3 to 12% of that of control in various experiments, after treatment with ara-C, 10 to 20 mg/kg; it then reboun...

An infant with pancytopenia was born to a mother who used the common immunosuppressant azathioprine (AZA). Maternal and neonatal blood levels of 6-thioguanine nucleotides (6TGN; metabolite of AZA) were 1890 and 1480 pmol/8 × 10(8) red blood cells, respectively. Maternal 6TGN levels could be useful in predicting neonatal pancytopenia.

Adenosine but not cytidine at 2 HIMdelayed metaphase some what. Nucleolar reconstruction was retarded in cells after treatment with adenosine, deoxyadenosine, and certain combinations of agents including deoxyribonueleosides. A nucleolar change resembling that induced by adenosine or 6-thioguanine was produced in interphasic cells by a combina tion of deoxyadenosine, deoxyguanosine, and deoxycy...

The deactivation mechanism of the cytotoxic 6-thioguanine, the 6-sulfur-substituted analogue of the canonical DNA base, is unveiled by ab initio calculations. Oxygen-by-sulfur substitution leads to efficient population of triplet states-the first step for generating singlet oxygen-which is responsible for its cytotoxicity.