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Chemical Compound Review

Hydrea     hydroxyurea

Synonyms: Cytodrox, Hydreia, Hydurea, Litaler, Litalir, ...
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Disease relevance of hydroxyurea


Psychiatry related information on hydroxyurea


High impact information on hydroxyurea

  • Unlike the response to DSBs, Mre11 and recombination proteins are not recruited to hydroxyurea-stalled replication forks unless the forks collapse [11].
  • Unlike conventional poly(A) polymerases, which act in the nucleus and indiscriminately polyadenylate all mRNA, Cid13 is a cytoplasmic enzyme that specifically targets suc22 mRNA that encodes a subunit of ribonucleotide reductase (RNR). cid13 mutants have reduced dNTP pools and are sensitive to hydroxyurea, an RNR inhibitor [12].
  • Proliferating cells depleted of Yph1p arrest in G(1) or G(2), with no cells in S phase, or significantly delay S phase progression after release from a hydroxyurea arrest [13].
  • BACKGROUND AND METHODS: On behalf of the Gynecologic Oncology Group, we performed a randomized trial of radiotherapy in combination with three concurrent chemotherapy regimens -- cisplatin alone; cisplatin, fluorouracil, and hydroxyurea; and hydroxyurea alone -- in patients with locally advanced cervical cancer [14].
  • Hydroxyurea-mediated DNA synthesis arrest of S phase MCF7 cells led to a loss of BRCA1 from these structures [15].

Chemical compound and disease context of hydroxyurea


Biological context of hydroxyurea


Anatomical context of hydroxyurea

  • Upon polyclonal stimulation of B lymphocytes or in proliferating B-lymphocyte-derived cell lines, the synthesis of XM1 is switched off, but it is reinduced by agents that arrest replication, such as mitomycin C, hydroxyurea, ultraviolet light or gamma irradiation [24].
  • The proportion of BFU-E normally engaged in DNA synthesis is low in adult B6 (C57BL/6) mice of genotype Fv2rr (resistant to Friend erythroleukemia virus), as shown by 3H-thymidine or hydroxyurea "cell suicide" experiments in vivo and vitro [25].
  • In contrast, hydroxyurea treatment was associated with a 3-to-25-fold increase in F reticulocytes, a 1.6-to-7-fold increase in F cells, and a 2.3-to-16-fold increase in the percentage of hemoglobin F [18].
  • Hydroxyurea inhibits human immunodeficiency virus-type 1 (HIV-1) DNA synthesis in activated peripheral blood lymphocytes by decreasing the amount of intracellular deoxynucleotides, thus suggesting that this drug has an antiviral effect [19].
  • Wild-type flies made a discrete choice that switched from one alternative to the other as the relative salience of color and shape cues gradually changed, but this ability was greatly diminished in mutant (mbm1) flies with miniature mushroom bodies or with hydroxyurea ablation of mushroom bodies [26].

Associations of hydroxyurea with other chemical compounds


Gene context of hydroxyurea

  • HU-induced phosphorylation is associated with increased catalytic activity of Spk1p [33].
  • In this study, we show that BRCA1 phosphorylation is only partially ATM dependent in response to IR and ATM independent in response to treatment with UV light, or the DNA replication inhibitors hydroxyurea (HU) and aphidicolin (APH) [34].
  • Furthermore, the absence of a functional Xrs2p complex leads to sensitivity to deoxynucleotide depletion and to an inability to efficiently slow down cell cycle progression in response to hydroxyurea [35].
  • Like BRCA1 and RAD51, BRCA2 relocates to PCNA+ replication sites following exposure of S phase cells to hydroxyurea or UV irradiation [36].
  • The critical role of Mrc1p in HU is therefore to promote fork recovery in a Rad53p-independent manner, presumably through the formation of a stable fork-pausing complex [37].

Analytical, diagnostic and therapeutic context of hydroxyurea


  1. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Charache, S., Terrin, M.L., Moore, R.D., Dover, G.J., Barton, F.B., Eckert, S.V., McMahon, R.P., Bonds, D.R. N. Engl. J. Med. (1995) [Pubmed]
  2. Preliminary observations on the therapy of the myeloid blast phase of chronic granulocytic leukemia with plicamycin and hydroxyurea. Koller, C.A., Miller, D.M. N. Engl. J. Med. (1986) [Pubmed]
  3. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. Cortelazzo, S., Finazzi, G., Ruggeri, M., Vestri, O., Galli, M., Rodeghiero, F., Barbui, T. N. Engl. J. Med. (1995) [Pubmed]
  4. Successful use of hydroxyurea in beta-thalassemia major. Arruda, V.R., Lima, C.S., Saad, S.T., Costa, F.F. N. Engl. J. Med. (1997) [Pubmed]
  5. Hydroxyurea in essential thrombocytosis. Van Genderen, P.J., Michiels, J.J. N. Engl. J. Med. (1995) [Pubmed]
  6. Centrophobism/thigmotaxis, a new role for the mushroom bodies in Drosophila. Besson, M., Martin, J.R. J. Neurobiol. (2005) [Pubmed]
  7. Cell proliferation in a peripheral target is required for the induction of central neurogenesis in the leech. Becker, T.S., Bothe, G., Harley, A.R., Macagno, E.R. J. Neurobiol. (1998) [Pubmed]
  8. Possible adrenal involvement in hydroxyurea toxicity defense mechanisms. Preziosi, P., Nunziata, A., Macrae, S., Ragazzoni, E., Vacca, M. Arch. Toxicol. Suppl. (1985) [Pubmed]
  9. Sickle cell telemedicine and standard clinical encounters: a comparison of patient satisfaction. Woods, K.F., Kutlar, A., Johnson, J.A., Waller, J.L., Grigsby, R.K., Stachura, M.E., Rahn, D.W. Telemedicine journal : the official journal of the American Telemedicine Association. (1999) [Pubmed]
  10. Hydroxyurea-associated squamous dysplasia. Sanchez-Palacios, C., Guitart, J. J. Am. Acad. Dermatol. (2004) [Pubmed]
  11. Choreography of the DNA damage response: spatiotemporal relationships among checkpoint and repair proteins. Lisby, M., Barlow, J.H., Burgess, R.C., Rothstein, R. Cell (2004) [Pubmed]
  12. Cid13 is a cytoplasmic poly(A) polymerase that regulates ribonucleotide reductase mRNA. Saitoh, S., Chabes, A., McDonald, W.H., Thelander, L., Yates, J.R., Russell, P. Cell (2002) [Pubmed]
  13. Yph1p, an ORC-interacting protein: potential links between cell proliferation control, DNA replication, and ribosome biogenesis. Du, Y.C., Stillman, B. Cell (2002) [Pubmed]
  14. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. Rose, P.G., Bundy, B.N., Watkins, E.B., Thigpen, J.T., Deppe, G., Maiman, M.A., Clarke-Pearson, D.L., Insalaco, S. N. Engl. J. Med. (1999) [Pubmed]
  15. Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage. Scully, R., Chen, J., Ochs, R.L., Keegan, K., Hoekstra, M., Feunteun, J., Livingston, D.M. Cell (1997) [Pubmed]
  16. Hematologic remission and cytogenetic improvement induced by recombinant human interferon alpha A in chronic myelogenous leukemia. Talpaz, M., Kantarjian, H.M., McCredie, K., Trujillo, J.M., Keating, M.J., Gutterman, J.U. N. Engl. J. Med. (1986) [Pubmed]
  17. Stimulation of F-cell production in patients with sickle-cell anemia treated with cytarabine or hydroxyurea. Veith, R., Galanello, R., Papayannopoulou, T., Stamatoyannopoulos, G. N. Engl. J. Med. (1985) [Pubmed]
  18. Treatment of sickle cell anemia with hydroxyurea and erythropoietin. Goldberg, M.A., Brugnara, C., Dover, G.J., Schapira, L., Charache, S., Bunn, H.F. N. Engl. J. Med. (1990) [Pubmed]
  19. Hydroxyurea as an inhibitor of human immunodeficiency virus-type 1 replication. Lori, F., Malykh, A., Cara, A., Sun, D., Weinstein, J.N., Lisziewicz, J., Gallo, R.C. Science (1994) [Pubmed]
  20. Long-term suppression of HIV-1 by hydroxyurea and didanosine. Lori, F., Jessen, H., Foli, A., Lisziewicz, J., Matteo, P.S. JAMA (1997) [Pubmed]
  21. Cytoplasmic pH and the regulation of the Dictyostelium cell cycle. Aerts, R.J., Durston, A.J., Moolenaar, W.H. Cell (1985) [Pubmed]
  22. Fission yeast cut5+, required for S phase onset and M phase restraint, is identical to the radiation-damage repair gene rad4+. Saka, Y., Yanagida, M. Cell (1993) [Pubmed]
  23. Spindle formation and chromatin condensation in cells blocked at interphase by mutation of a negative cell cycle control gene. Osmani, S.A., Engle, D.B., Doonan, J.H., Morris, N.R. Cell (1988) [Pubmed]
  24. A B-lymphocyte-specific high-turnover protein: constitutive expression in resting B cells and induction of synthesis in proliferating cells. Rahmsdorf, H.J., Mallick, U., Ponta, H., Herrlich, P. Cell (1982) [Pubmed]
  25. A washable macromolecule from Fv2rr marrow negatively regulates DNA synthesis in erythropoietic progenitor cells BFU-E. Axelrad, A.A., Croizat, H., Eskinazi, D. Cell (1981) [Pubmed]
  26. Choice behavior of Drosophila facing contradictory visual cues. Tang, S., Guo, A. Science (2001) [Pubmed]
  27. Two genes differentially regulated in the cell cycle and by DNA-damaging agents encode alternative regulatory subunits of ribonucleotide reductase. Elledge, S.J., Davis, R.W. Genes Dev. (1990) [Pubmed]
  28. The requirement for DNA synthesis and gene expression in the generation of cytotoxicity in vitro. Nedrud, J., Touton, M., Clark, W.R. J. Exp. Med. (1975) [Pubmed]
  29. Inhibition of tumor cell ribonucleotide reductase by macrophage-derived nitric oxide. Kwon, N.S., Stuehr, D.J., Nathan, C.F. J. Exp. Med. (1991) [Pubmed]
  30. Radiosensitizing nucleosides. McGinn, C.J., Shewach, D.S., Lawrence, T.S. J. Natl. Cancer Inst. (1996) [Pubmed]
  31. Mechanism of Hb F stimulation by S-stage compounds. In vitro studies with bone marrow cells exposed to 5-azacytidine, Ara-C, or hydroxyurea. Galanello, R., Stamatoyannopoulos, G., Papayannopoulou, T. J. Clin. Invest. (1988) [Pubmed]
  32. Hydroxyurea nitrosylates and activates soluble guanylyl cyclase in human erythroid cells. Cokic, V.P., Andric, S.A., Stojilkovic, S.S., Noguchi, C.T., Schechter, A.N. Blood (2008) [Pubmed]
  33. Spk1/Rad53 is regulated by Mec1-dependent protein phosphorylation in DNA replication and damage checkpoint pathways. Sun, Z., Fay, D.S., Marini, F., Foiani, M., Stern, D.F. Genes Dev. (1996) [Pubmed]
  34. Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress. Tibbetts, R.S., Cortez, D., Brumbaugh, K.M., Scully, R., Livingston, D., Elledge, S.J., Abraham, R.T. Genes Dev. (2000) [Pubmed]
  35. The yeast Xrs2 complex functions in S phase checkpoint regulation. D'Amours, D., Jackson, S.P. Genes Dev. (2001) [Pubmed]
  36. Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. Chen, J., Silver, D.P., Walpita, D., Cantor, S.B., Gazdar, A.F., Tomlinson, G., Couch, F.J., Weber, B.L., Ashley, T., Livingston, D.M., Scully, R. Mol. Cell (1998) [Pubmed]
  37. Mrc1 and Tof1 promote replication fork progression and recovery independently of Rad53. Tourrière, H., Versini, G., Cordón-Preciado, V., Alabert, C., Pasero, P. Mol. Cell (2005) [Pubmed]
  38. Augmentation of fetal-hemoglobin production in anemic monkeys by hydroxyurea. Letvin, N.L., Linch, D.C., Beardsley, G.P., McIntyre, K.W., Nathan, D.G. N. Engl. J. Med. (1984) [Pubmed]
  39. The insertion of DNA into vaccinia virus. Morgan, C. Science (1976) [Pubmed]
  40. Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage. Kim, S.T., Xu, B., Kastan, M.B. Genes Dev. (2002) [Pubmed]
  41. Hematopoietic stem cells in Friend murine leukemia virus-infected mice undergoing chemotherapy: remission and relapse of erythropoietin-independent erythropoiesis induced by hydroxyurea. Seidel, H.J., Opitz, U. J. Natl. Cancer Inst. (1979) [Pubmed]
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