Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pluripotent embryonic carcinoma cells of line P19 established from undifferentiated cells of the early mouse embryo and their differentiated progeny, the epithelioid ectoderm-like EPI-7 cells, were investigated for the induction of mutations at the HPRT locus by the alkylating agent N-ethyl-N-nitrosourea (ENU). We showed that the cytotoxic effects of ENU after a 5-h treatment were lower in undifferentiated P19 cells than in differentiated EPI-7 cells. The IC50 values of ENU in the two cell lines amounted to 0.6 mg/ml and 0.09 mg/ml for P19 and EPI-7 cells, respectively. The induction of 6-thioguanine-resistant mutants by ENU (1.0 mg/ml) determined after an expression time of 8 days for both cell lines resulted in similar mutation frequencies. Using expression times of 8 days for P19 and 11.75 days for EPI-7 cells, taking into account the longer generation time of differentiated EPI-7 cells (13.7 +/- 3.6 h) in comparison to undifferentiated P19 cells (9.3 +/- 0.9 h), ENU induced significantly higher mutant frequencies in EPI-7 cells (4865 mutants/10(6) cells) than in P19 cells (282 mutants/10(6) cells). Our results and data from the literature on UV irradiation-induced repair support the idea that the induction of lower mutation frequencies in embryonic cells may correlate with different proliferation capacities, cell cycle parameters and/or different mechanisms of DNA repair in embryonic stem cells and differentiated cells, respectively.
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PMID:Lower mutation frequencies are induced by ENU in undifferentiated embryonic cells than in differentiated cells of the mouse in vitro. 751 73

Stable, oxygen-resistant cell lines (O2R) were isolated from P19 and P19H22 (APRT hemizygote) mouse embryonic carcinoma cells by serial exposures of increasing durations to 95% O2. Neurally differentiated progeny were also oxygen-resistant. P19O2R exhibited reduced oxygen-mediated micronucleation and a 10- to 20-fold reduction of the forward mutation rate at the HPRT locus in 20% O2. P19H22O2R cells showed reduced frequencies of colonies resistant to 2,6-diaminopurine. The modal karyotype of P19O2R was identical to that of a nonmodal karyotype present in the parental line [39,X,-Y, add(14)]. There was no evidence of enhanced resistance to ionizing radiation. We conclude that this general approach, when applied to pluripotent embryonic stem cells, has the potential to lead to the synthesis of antimutator strains of mice.
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PMID:Oxygen-resistant multipotent embryonic carcinoma cell lines exhibit antimutator phenotypes. 782 58

Pluripotent undifferentiated embryonic carcinoma cells of line P19 and their differentiated progeny, epithelioid ectoderm-like EPI-7 cells, showed different responses to mitomycin C (MMC) with respect to induction of micronuclei, mutations at the HPRT-locus and cell cycle control. Cytotoxic effects of MMC after a 5-h treatment were lower in undifferentiated P19 cells than in differentiated EPI-7 cells with IC50 values of 1.3 and 0.25 microM for P19 and EPI-7 cells, respectively. MMC did not induce 6-thioguanine-resistant mutants in P19 cells but significantly increased the mutation frequency in EPI-7 cells with concentrations of 0.25, 0.5 and 1.0 microM MMC. Micronuclei determined by flow-cytometry were induced by MMC in both cell lines at equitoxic concentrations of 4.5 (P19) and 0.75 (EPI-7) microM, reducing the viability in both cell lines to 10%. Whereas the induction of micronuclei in P19 cells was maximal 28 h after treatment and declined thereafter, micronucleus induction peaked 48 h post treatment in EPI-7 cells and remained significantly increased even 67 h after the treatment. Flow-cytometric determination of the distribution of MMC-treated P19 and EPI-7 within the cell cycle revealed a distinct G2/M-block in P19 cells, whereas EPI-7 cells showed normal progression through S-phase and a negligible G2/M-block. Therefore, we conclude that the lower effectivity of MMC to induce gene mutations and micronuclei in P19 cells seemed to be correlated with a more efficient cell cycle control in undifferentiated compared to differentiated EPI-7 cells.
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PMID:Low mutagenic effects of mitomycin C in undifferentiated embryonic P19 cells are correlated with efficient cell cycle control. 869 96

The aim of our study was to characterize mouse embryonal carcinoma (EC) cells P19 in different stages of retinoic acid induced neurodifferentiation by two methods, immunocytochemistry and RT qPCR. The characterization of the cells is crucial before any transplantation into any model, e.g. in our case into the mouse brain with the aim to treat a neurodegenerative disease. Specific protein markers (MAP-2, OCT-4, FORSE-1) were detected by immunocytochemistry in the cell cultures. The mRNA expression levels of PAX-6, MASH-1, Brachyury, GATA-4 and AFP were determined by RT qPCR method. HPRT was used as a housekeeping gene. The degree of differentiation can be characterized by expression of analyzed genes. The presence of OCT-4 and FORSE-1 proteins in undifferentiated pluripotent cells and the presence of dendrite specific MAP-2 in neuroprogenitors was detected. The expression levels of PAX-6 and MASH-1 increased and expression of Brachyury decreased during the neurodifferentiation process. The expression levels of GATA-4 and AFP were the highest after induction of differentiation with retinoic acid. Detailed characterization of cells before transplantation experiments can contribute to better understanding of their effect.
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PMID:Characterization of P19 cells during retinoic acid induced differentiation. 2118 68