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.

The incorporation of 6-thioguanine (S6G) into DNA is a prerequisite for its cytotoxic action, but duplex structure is not significantly perturbed by the presence of the lesion [J. Bohon and C. R. de los Santos (2003) Nucleic Acids Res., 31, 1331-1338]. It is therefore possible that the mechanism of cytotoxicity relies on a loss of stability rather than a pathway involving direct structural reco...

We have examined the ability of SV40 to induce changes in drug or temperature resistance in mouse, hamster, and mouse-human hybrid cells. SV40 induced a substantial increase of cells resistant to 5-bromodeoxyuridine + trifluorothymidine in Balb/c 3T3 cells and induced an increase of hybrid cells resistant to 6-thioguanine. SV40 was found to be nonmutagenic or weakly mutagenic in other test syst...

of MMPR forms rapidly to levels of 1 to 2 mM in the tumor cells, and the steady-state levels of 5-phosphoribosyl 1-pyrophosphate increase 4to 5-fold in 6 to 12 hr. This permits a significantly greater synthesis of 6-thioguanosine monophosphate (6-thioGMP) after injection of 6-thioguanine. These findings are similar to those in previous reports concerning the synergism between 6-mercaptopurine a...

The thiopurine antimetabolites 6-thioguanine and 6-mercaptopurine are important chemotherapeutic drugs in the treatment of childhood acute lymphoblastic leukaemia. Measurement of metabolites of these thiopurines is important because correlations exist between levels of these metabolites and the prognosis in childhood acute lymphoblastic leukaemia. The reversed-phase method for the determination...

Present work describes the fluorescence spectroscopy determination of (6-TG) using silver nanoparticles (AgNPs). The acridine could be electrostatically adsorbed to the surface of the citrate-stabilized silver nanoparticles. Upon addition of 6-TG, the acridine is replaced from the surface of AgNPs which induce the aggregation of AgNPs. Under optimum condition, the fluorescence intensity enhance...

The effects of 9-butyl-6-thioguanine (9-BTG)1 on the utilization of preformed purines by the Ehrlich ascites tumor were studied in vivo.The results showed that 9-BTG inhibited the utilization of preformed purines for DNA synthesis under conditions in which UNA synthesis and the incorporation of glycine into proteins and nucleic acids were unaffected. Studies on the incorporation of glycine-2-C1...