Although the thiopurine drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are well established agents for the treatment of leukemia, controversies remain regarding their main mode of action. Previous evidence has suggested that although 6-TG exerts a cytotoxic effect through incorporation of 6-thioguanine nucleotides into newly synthesized DNA (DNA-TGN), an important component of the mode ...

Here we report the in vitro selection of fast ribozymes capable of promoting the synthesis of a purine nucleotide (6-thioguanosine monophosphate) from tethered 5-phosphoribosyl 1-pyrophosphate (PRPP) and 6-thioguanine ((6S)Gua). The two most proficient purine synthases have apparent efficiencies of 284 and 230 M(-1) min(-1) and are both significantly more efficient than pyrimidine nucleotide sy...

Loss of DNA mismatch repair is a common finding in many types of sporadic human cancers as well as in tumors arising in patients with hereditary nonpolyposis colon cancer. The effect of the loss of DNA mismatch repair activity on sensitivity to a panel of commonly used chemotherapeutic agents was tested using one pair of cell lines proficient or deficient in mismatch repair due to loss of hMSH2...

Using an in vitro assay system, polybrominated biphenyl (PBB) was assessed for its ability to inhibit metabolic cooperation between 6-thioguanine sensitive and resistant Chinese hamster V79 cells. Using a nonlethal range of the chemical, PBB was shown to inhibit metabolic cooperation (a form of cell-cell communication) in a manner similar to other known tumor promoters. Results suggest that PBB...

A series of phosphinegold(I) thionucleobase analogues, [R(3)PAu(SR(x))] (R = Et, Ph or chexyl; HSR(1) = 2-mercaptobenzoic acid, HSR(2) = 2-thiouracil, HSR(3) = 6-mercaptopurine and HSR(4) = 6-thioguanine) have been examined for their in vitro cytotoxicity in L1210 murine leukemia cells in culture. The range of ID(50) values (continuous 48 h exposure) for the complexes is 0.041 - 0.131 muM. The ...

Thiopurines have been used in inflammatory bowel disease (IBD) for >30 years, and measurements of both thiopurine methyltransferase (TPMT) and thiopurine (TP) metabolites, 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP), have been readily available. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Committee on Inflammatory Bowe...

The German cooperative study group for childhood acute lymphoblastic leukemia (COALL-92) was designed to examine the clinical effectiveness of thioguanine (TG) versus mercaptopurine (MP) in maintenance treatment of childhood acute lymphoblastic leukemia (ALL) in a randomized multicenter trial. TG and MP are prodrugs and have to be converted intracellularly to 6-thioguanine nucleotides (TGNs) fo...