Disease relevance of Tabloid

• A low metastatic, thioguanine-resistant murine T lymphoma line (EbTGR) was hybridized in vitro, with the help of polyethylene glycol, with syngeneic bone marrow-derived macrophages [1].
• Modified chemotherapy with carmustine, cytarabine, cyclophosphamide, and 6-thioguanine (BACT) and autologous bone marrow transplantation in 24 poor-risk patients with acute lymphoblastic leukemia [2].
• PALA, ara-C, and TG failed to demonstrate regressing activity against the spontaneous murine breast tumors [3].
• 6-thioguanine can cause serious liver injury in inflammatory bowel disease patients [4].
• The administration of busulphan and thioguanine in combination is likely to be associated with the development of NRH, with portal hypertension and oesophageal varices occurring in a substantial proportion of cases [5].

High impact information on Tabloid

• The thioguanine-resistant cell line 281-1-4, derived from SVT2/S, remained stable on subculture but a chloramphenicol-resistant mutant, 107-6-4, derived from 281-1-4, was highly unstable [6].
• The frequencies of transformations of primary human and Chinese hamster fibroblasts have been compared with the spontaneous and induced frequencies of mutation for resistance to thioguanine and ouabain, and for ability to use fructose, using the carcinogens benzo (alpha) pyrene and urethane [7].
• The frequencies and the rates of segregation of the Emtr and Thgr (thioguanine-resistant, an X-linked recessive mutation) markers were determined from hybrids constructed between an Emtr-Thgr CHO cell line and various other Chinese hamster lines (V79, M3-1, CHO, GM7S, CHW and CHL) [8].
• By selecting variants of Chinese hamster cells that were resistant to 6-thioguanine at 39 degrees C, but which would continue to grow in HAT medium at 33 degrees C, we have isolated cell lines with thermosensitive phenotypes [9].
• The thioguanine-resistant T cell stably lack hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity, suggesting that they are somatic equivalents in normal individuals to cells from individuals with the X-chromosomal hprt Lesch-Nyhan germinal mutation [10].

Chemical compound and disease context of Tabloid

• 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 [11].
• A subclone of these simian virus 40 (SV40)-transformed cells (6TGR-SV-tfm) selected in 6-thioguanine and lacking hypoxanthine phosphoribosyltransferase was used to produce a series of mouse--human hybrids containing the normal human X chromosome or various X autosome-translocation chromosomes (expressing only segments of the human X chromosome) [12].
• Hybrids were made between a ouabain-resistant, thioguanine-resistant human lymphoma line able to remove O6-methylguanine from its DNA (Mex+) and human lymphoblastoid lines deficient in this capability (Mex-) [13].
• One-hundred and seven patients with acute myelogenous leukemia (AML) ranging in age from 15 to 82 yr who were previously untreated, received a 70 day high-dose remission induction regimen consisting of daunorubicin, cytarabine, and thioguanine (TAD) [14].
• To obtain further evidence for the role of MMR on 6TG and MNNG toxicity, we isolated an MNNG-resistant revertant clone, M2, from the MNNG-sensitive, MMR-proficient HCT116 + chr3 cell line and characterized the MMR activity, hMLH1 status, and 6TG response [15].

Biological context of Tabloid

• In V-79 Chinese hamster cells we have been measuring DNA damage by alkaline elution, mutation induction as detected by 6-thioguanine resistance, and cytotoxicity as detected by colony formation for different physical and chemical agents [16].
• Do radiation-induced thioguanine-resistant mutants of cultured mammalian cells arise by HGPRT gene mutation or X-chromosome rearrangement [17]?
• This mutant cell line, designated CEM-T15, was derived from the human T cell line CEM after chemical mutagenesis with ethane methylsulfonate and subsequent culture in medium containing 6-thioguanine [18].
• Experiments on cross-resistance and delayed cytotoxicity showed differences in the cytotoxicities of TG-Pt(II) and SeG-Pt(II): TG-Pt(II) exerted its activity through its hydrolysis product thioguanine, whereas SeG-Pt(II) compound was cytotoxic itself [19].
• Suppression of tumorigenicity is relieved by selecting cells which have lost the t(X;11) chromosome by growth in medium containing 6-thioguanine (6-TG) [20].

Anatomical context of Tabloid

• Several years ago we proposed that 6-thioguanine-resistant T lymphocytes, present at low frequencies in human peripheral blood, might be useful markers of in vivo somatic mutation [10].
• The mean incidence in age- and sex-matched controls was 2.1 X 10(-4), so approximately eight times the normal number of 6-thioguanine-resistant lymphocytes were detected in Bloom's syndrome blood [21].
• Primary rat bladder epithelial cells were cocultivated with Chinese hamster V79 cells in the presence of carcinogens, and the induction of 6-thioguanine resistance in the V79 cells was used as a marker of cell-mediated mutagenesis [22].
• Steady state of erythrocyte 6-thioguanine nucleotide and complete response occurred earlier than previously reported [23].
• In contrast to its inhibition of neurite regeneration and ornithine decarboxylase induction, 6-thioguanine did not suppress NGF-dependent induction of c-fos mRNA expression [24].

Associations of Tabloid with other chemical compounds

• Azathioprine, an immunosuppressant used in organ transplantation, is partly converted to thioguanine [25].
• Mutants resistant to 6-thioguanine were induced in pseudotetraploid hybrid Chinese hamster cells homozygous wild-type at the locus for hypoxanthine phophoribosyl transferase but heterozygous for the linked marker glucose-6-phosphate dehydrogenase [26].
• The incidence of lymphocytes resistant to the purine analog 6-thioguanine was studied in seven patients with Bloom's syndrome [21].
• Of the six children, four had erythrocyte concentrations of thioguanine nucleotide metabolites higher than the 70th percentile for the entire cohort, and three had a genetic defect in thiopurine catabolism [27].
• 28 adult patients with acute myeloid leukaemia (A.M.L.) received T.A.D., a high-dose sequential chemotherapeutic remission-induction regimen consisting of 7-day courses of cytosine arabinoside, 6-thioguanine, and daunorubicin [28].

Gene context of Tabloid

• ES cells homozygous for the Msh2 mutation displayed increased resistance to killing by the cytotoxic drug 6-thioguanine (6TG), indicating that the 6TG cytotoxic mechanism is mediated by Msh2 [29].
• Selective radiosensitization of drug-resistant MutS homologue-2 (MSH2) mismatch repair-deficient cells by halogenated thymidine (dThd) analogues: Msh2 mediates dThd analogue DNA levels and the differential cytotoxicity and cell cycle effects of the dThd analogues and 6-thioguanine [30].
• A role for the Mut L homologue-1 (MLH1) protein, a necessary component of DNA mismatch repair (MMR), in G2-M cell cycle checkpoint arrest after 6-thioguanine (6-TG) exposure was suggested previously [31].
• Alternative immunosuppressive drugs, particularly 6-thioguanine, should be considered for AZA-intolerant patients with ITPase deficiency [32].
• Human CYP2A6, which is known to activate NNK to a mutagen, was lipofected via a retroviral vector into the Chinese hamster ovary AS52 cell line, which contains the bacterial gpt gene and can be mutated to 6-thioguanine resistance [33].
• The association of lower TPMT activity with thioguanine-related liver damage could provide a means of identifying at-risk patients [34].

Analytical, diagnostic and therapeutic context of Tabloid

• We now report that in vivo-derived thioguanine-resistant T-cell colonies from a single normal individual show a variety of hprt structural alterations, as determined by Southern blot analysis [10].
• Association of 6-thioguanine nucleotide levels and inflammatory bowel disease activity: a meta-analysis [35].
• We are unaware of any published reports of veno-occlusive disease of the liver after treatment with either 6-thioguanine or cytosine arabinoside [36].
• DNA was extracted from 6-thioguanine-resistant colonies and amplified by the polymerase chain reaction (PCR) using primers flanking Hprt exon 3 [37].
• No 6-thioguanine-resistant mutants could be induced by either gamma- or UV-irradiation in these cells, suggesting that error-prone repair pathways for damage induced by these agents may contain a common ligation step in human cells [38].

References