NTP‐CERHR Expert Panel Report on the reproductive and developmental toxicity of hydroxyurea
2007; Wiley; Volume: 80; Issue: 4 Linguagem: Inglês
10.1002/bdrb.20123
ISSN2472-1727
AutoresErica L. Liebelt, Sophie J. Balk, Willem D. Faber, Jeffrey W. Fisher, Claude L. Hughes, Sophie Lanzkron, Kerry Lewis, Francesco Marchetti, Harihara M. Mehendale, John M. Rogers, Aziza Shad, Richard G. Skalko, Edward J. Stanek,
Tópico(s)Prenatal Screening and Diagnostics
ResumoBirth Defects Research Part B: Developmental and Reproductive ToxicologyVolume 80, Issue 4 p. 259-366 Expert Panel Report NTP-CERHR Expert Panel Report on the reproductive and developmental toxicity of hydroxyurea†‡ Erica L. Liebelt, Erica L. Liebelt University of Alabama, Birmingham, ALSearch for more papers by this authorSophie J. Balk, Sophie J. Balk Albert Einstein College of Medicine, Bronx, NYSearch for more papers by this authorWillem Faber, Willem Faber Willem Faber Toxicology Consulting, LLC, Victor, NYSearch for more papers by this authorJeffrey W. Fisher, Jeffrey W. Fisher University of Georgia, Athens, GASearch for more papers by this authorClaude L. Hughes, Claude L. Hughes RTI International, Research Triangle Park, NCSearch for more papers by this authorSophie M. Lanzkron, Sophie M. Lanzkron Johns Hopkins University, Baltimore, MDSearch for more papers by this authorKerry M. Lewis, Kerry M. Lewis Howard University, Washington, DCSearch for more papers by this authorFrancesco Marchetti, Francesco Marchetti Lawrence Berkeley National Laboratory, Berkeley, CASearch for more papers by this authorHarihara M. Mehendale, Harihara M. Mehendale University of Louisiana, Monroe, LASearch for more papers by this authorJohn M. Rogers, John M. Rogers Environmental Protection Agency, Research Triangle Park, NCSearch for more papers by this authorAziza T. Shad, Aziza T. Shad Georgetown University, Washington, DCSearch for more papers by this authorRichard G. Skalko, Richard G. Skalko East Tennessee State University, Johnson City, TN Dr. Skalko was unable to participate in the Expert Panel meeting but participated in the drafting and review of the report before and after the meetingSearch for more papers by this authorEdward J. Stanek, Corresponding Author Edward J. Stanek [email protected] University of Massachusetts, Amherst, MAMichael D. Shelby, PhD, NIEHS EC-32, PO Box 12233, Research Triangle Park, NC 27709Search for more papers by this author Erica L. Liebelt, Erica L. Liebelt University of Alabama, Birmingham, ALSearch for more papers by this authorSophie J. Balk, Sophie J. Balk Albert Einstein College of Medicine, Bronx, NYSearch for more papers by this authorWillem Faber, Willem Faber Willem Faber Toxicology Consulting, LLC, Victor, NYSearch for more papers by this authorJeffrey W. Fisher, Jeffrey W. Fisher University of Georgia, Athens, GASearch for more papers by this authorClaude L. Hughes, Claude L. Hughes RTI International, Research Triangle Park, NCSearch for more papers by this authorSophie M. Lanzkron, Sophie M. Lanzkron Johns Hopkins University, Baltimore, MDSearch for more papers by this authorKerry M. Lewis, Kerry M. Lewis Howard University, Washington, DCSearch for more papers by this authorFrancesco Marchetti, Francesco Marchetti Lawrence Berkeley National Laboratory, Berkeley, CASearch for more papers by this authorHarihara M. Mehendale, Harihara M. Mehendale University of Louisiana, Monroe, LASearch for more papers by this authorJohn M. Rogers, John M. Rogers Environmental Protection Agency, Research Triangle Park, NCSearch for more papers by this authorAziza T. Shad, Aziza T. Shad Georgetown University, Washington, DCSearch for more papers by this authorRichard G. Skalko, Richard G. Skalko East Tennessee State University, Johnson City, TN Dr. Skalko was unable to participate in the Expert Panel meeting but participated in the drafting and review of the report before and after the meetingSearch for more papers by this authorEdward J. Stanek, Corresponding Author Edward J. Stanek [email protected] University of Massachusetts, Amherst, MAMichael D. Shelby, PhD, NIEHS EC-32, PO Box 12233, Research Triangle Park, NC 27709Search for more papers by this author First published: 21 August 2007 https://doi.org/10.1002/bdrb.20123Citations: 61 † This article is a U.S. Government work and, as such, is in the public domain in the United States of America. ‡ Prepared With the Support of CERHR Staff: NTP/NIEHS, Michael Shelby, Ph.D. (Director, CERHR), Paul M.D. Foster, Ph.D. (Deputy Director, CERHR), Allen Dearry, Ph.D. (Interim Associate Director, NTP), Mary Wolfe, Ph.D. (NTP Liaison and Scientific Review Office); Sciences International, Inc., Anthony Scialli, M.D. (Principal Scientist), Annette Iannucci, M.S. (Toxicologist), Gloria Jahnke, D.V.M. (Toxicologist), Elizabeth Cho-Fertikh, Ph.D. (Toxicologist), Vera Jurgenson, M.S. (Research Associate).This report is prepared according to the Guidelines for CERHR Panel Members established by NTP/NIEHS. The guidelines are available on the CERHR web site (http://cerhr.niehs.nih.gov/). The format for Expert Panel Reports includes synopses of studies reviewed, followed by an evaluation of the Strengths/Weaknesses and Utility (Adequacy) of the study for CERHR evaluation. Statements and conclusions made under Strengths/Weaknesses and Utility evaluations are those of the Expert Panel and are prepared according to the NTP/NIEHS guidelines. In addition, the Panel often makes comments or notes limitations in the synopses of the study. Bold, square brackets are used to enclose such statements. As discussed in the guidelines, square brackets are used to enclose key items of information not provided in a publication, limitations noted in the study, conclusions that differ from those of the authors, and conversions or analyses of data conducted by the Panel. The findings and conclusions of this report are those of the expert panel and should not be construed to represent the views of the National Toxicology Program. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL REFERENCES American College of Obstetricians and Gynecologists. 2005. Practice bulletin No. 64: hemoglobinopathies in pregnancy. Obstet Gynecol 106: 203– 211. Adamson RH, Ague SL, Hess SM, Davidson JD. 1965. The distribution, excretion, and metabolism of hydroxyurea-C14. J Pharmacol Exp Ther 150: 322– 327. Adlard BP, Dobbing J. 1975. Maze learning by adult rats after inhibition of neuronal multiplication in utero. Pediatr Res 9: 139– 142. Aliverti V, Bonanomi L, Giavini E. 1980. Hydroxyurea as a reference standard in teratological screening. Comparison of the embryotoxic and teratogenic effects following single intraperitoneal or repeated oral administrations to pregnant rats. Arch Toxicol Suppl 4: 239– 247. Al-Jam'a AH, Al-Dabbous IA. 2002. Hydroxyurea in sickle cell disease patients from Eastern Saudi Arabia. Saudi Med J 23: 277– 281. Altura RA, Wang WC, Wynn L, Altura BM, Altura BT. 2002. Hydroxyurea therapy associated with declining serum levels of magnesium in children with sickle cell anemia. J Pediatr 140: 565– 569. Amortegui AJ, Feinberg SS, Figallo EM. 1976. Postnatal effects of chemically induced intrauterine growth retardation on some hematological values in the rat. Biol Neonate 29: 216– 221. Amortegui AJ, Klionsky B, Surti U, Coyne A. 1983. Experimental intrauterine fetal growth retardation in the rat: effect of a single dose of hydroxyurea or cycloheximide on the fetus at term. Prog Clin Biol Res 140: 13– 26. Amrolia PJ, Almeida A, Halsey C, Roberts IA, Davies SC. 2003. Therapeutic challenges in childhood sickle cell disease. Part 1. current and future treatment options. Br J Haematol 120: 725– 736. Archibong AE, Powell A, Hills ER. 2000. Male fertility as affected by hydroxyurea: clinical application/contraceptive potential. Adv Reprod 4: 36a. Asano Y, Ariyuki F, Higaki K. 1983. Behavioral effects of hydroxyurea exposure during organogenetic period of rats. Congenit Anom 23: 279– 289. Asano Y, Ariyuki F, Higaki K. 1985. Behavioral effects of hydroxyurea exposure during organogenetic period of the Sprague-Dawley rats. Congenit Anom 25: 23– 28. Asano Y, Okaniwa A. 1987. In utero morphologic effects of hydroxyurea on the fetal development in Sprague-Dawley rats. Jikken Dobutsu 36: 143– 149. Avlasevich SL, Bryce SM, Cairns SE, Dertinger SD. 2006. In vitro micronucleus scoring by flow cytometry: differential staining of micronuclei versus apoptotic and necrotic chromatin enhances assay reliability. Environ Mol Mutagen 47: 56– 66. Awogi T, Fukazawa H, Tao K. 1987. Induction of micronuclei in rat fetuses by hydroxyurea. Mutat Res 182: 357. Baarends WM, Hoogerbrugge JW, Post M, Visser JA, De Rooij DG, Parvinen M, Themmen AP, Grootegoed JA. 1995. Anti-mullerian hormone and anti-mullerian hormone type II receptor messenger ribonucleic acid expression during postnatal testis development and in the adult testis of the rat. Endocrinology 136: 5614– 5622. Bakanay SM, Dainer E, Clair B, Adekile A, Daitch L, Wells L, Holley L, Smith D, Kutlar A. 2005. Mortality in sickle cell patients on hydroxyurea therapy. Blood 105: 545– 547. Bantle JA, Burton DT, Dawson DA, Dumont JN, Finch RA, Fort DJ, Linder G, Rayburn JR, Buchwalter D, Maurice MA, et al. 1994. Initial interlaboratory validation study of FETAX: phase I testing. J Appl Toxicol 14: 213– 223. Barden EM, Kawchak DA, Ohene-Frempong K, Stallings VA, Zemel BS. 2002. Body composition in children with sickle cell disease. Am J Clin Nutr 76: 218– 225. Barr M Jr, Beaudoin AR. 1981. An exploration of the role of hydroxyurea injection time in fetal growth and teratogenesis in rats. Teratology 24: 163– 167. Baumann M, Sander K. 1984. Bipartite axiation follows incomplete epiboly in zebrafish embryos treated with chemical teratogens. J Exp Zool 230: 363– 376. Baykal C, Zengin N, Coskun F, Guler N, Ayhan A. 2000. Use of hydroxyurea and alpha-interferon in chronic myeloid leukemia during pregnancy: a case report. Eur J Gynaecol Oncol 21: 89– 90. Beliles RP, Makris NG, Scott WJ. 1991. Consideration of pharmacokinetics and temporal sensitivity for hydroxyurea in relation to teratogenic potential. J Am Coll Toxicol 10: 269– 278. Belt RJ, Haas CD, Kennedy J, Taylor S. 1980. Studies of hydroxyurea administered by continuous infusion: toxicity, pharmacokinetics, and cell synchronization. Cancer 46: 455– 462. Bigot K, De Lange J, Archer G, Clothier R, Bremer S. 1999. The relative semi-quantification of mRNA expression as a useful toxicological endpoint for the identification of embryotoxic-teratogenic substances. Toxicol In Vitro 13: 619– 623. Bodit F, Stoll R, Maraud R. 1966. [Action of hydroxyurea, of semicarbazide and of related substances on the development of the chick embryo]. C R Seances Soc Biol Fil 160: 960– 963. Bournias-Vardiabasis N. 1990. Drosophila melanogaster embryo cultures: an in vitro teratogen assay. Altern Lab Anim 18: 291– 300. Bower M, Rustin GJ, Newlands ES, Holden L, Short D, Foskett M, Bagshawe KD. 1998. Chemotherapy for gestational trophoblastic tumours hastens menopause by 3 years. Eur J Cancer 34: 1204– 1207. Brachet J. 1967. Effects of hydroxyurea on development and regeneration. Nature 214: 1132– 1133. Braga LB, Ferreira AC, Guimaraes M, Nazario C, Pacheco P, Miranda A, Picanco I, Seixas T, Rosado L, Amaral JM. 2005. Clinical and laboratory effects of hydroxyurea in children and adolescents with sickle cell anemia: a Portuguese hospital study. Hemoglobin 29: 171– 180. Bremer S, van Dooren M, Paparella M, Kossolov E, Fleischmann B, Hescheler J. 1999. Establishment of an embryotoxicity assay with green fluorescence protein-expressing embryonic cell-derived cardiomyocytes. Altern Lab Anim 27: 471– 484. Bristol-Myers-Squibb. 1999. HYDREA. Bristol-Myers-Squibb. 2001a. DROXIA. Bristol-Myers-Squibb. 2001b. HYDREA. Bristol-Myers-Squibb. 2002. DROXIA. Bristol-Myers-Squibb. 2004. HYDREA. Bristol-Myers-Squibb. 2005a. Droxia (hydroxyurea capsules, USP). Available at http://www.bms.com/cgi-bin/anybin.pl?sql=select%20PPI%20from%20TB_PRODUCT_PPI%20where%20PPI_SEQ=50&=PPI. Bristol-Myers-Squibb. 2005b. Hydrea (hydroxyurea capsules, USP). Available at http://www.bms.com/cgi-bin/anybin.pl?sql=select%20PPI%20from%20TB_PRODUCT_PPI%20where%20PPI_SEQ=72&key=PPI. Brock WA, Trostle PK, Meistrich ML. 1980. Meiotic synthesis of testis histones in the rat. Proc Natl Acad Sci USA 77: 371– 375. Brock WA, Trostle-Weige PK, Williams M, Meistrich ML. 1983. Histone and DNA synthesis in differentiating and rapidly proliferating cells in vivo and in vitro. Cell Differ 12: 47– 55. Bruce WR, Heddle JA. 1979. The mutagenic activity of 61 agents as determined by the micronucleus, Salmonella, and sperm abnormality assays. Can J Genet Cytol 21: 319– 334. Brunner RL, McLean M, Vorhees CV, Butcher RE. 1978. A comparison of behavioral and anatomical measures of hydroxyurea induced abnormalities. Teratology 18: 379– 384. Bunn HF. 1997. Pathogenesis and treatment of sickle cell disease. N Engl J Med 337: 762– 769. Butcher RE, Scott WJ, Kazmaier K, Ritter EJ. 1973. Postnatal effects in rats of prenatal treatment with hydroxyurea. Teratology 7: 161– 165. Byrd DC, Pitts SR, Alexander CK. 1999. Hydroxyurea in two pregnant women with sickle cell anemia. Pharmacotherapy 19: 1459– 1462. Carnero A, Jimenez R, Burgos M, Sanchez A, Diaz de la Guardia R. 1991. The synaptic sequence in hydroxyurea-treated spermatocytes of Pitymys duodecimcostatus (Rodentia, Microtidae). Cytogenet Cell Genet 56: 69– 73. Celiloglu M, Altunyurt S, Undar B. 2000. Hydroxyurea treatment for chronic myeloid leukemia during pregnancy. Acta Obstet Gynecol Scand 79: 803– 804. Chahoud I, Kuriyama SN, Paumgartten FJ. 2002. Maternal protein-and-energy restriction reduces the developmental toxicity of cyclophosphamide and hydroxyurea in rats. Toxicology 179: 137– 149. Chaine B, Neonato MG, Girot R, Aractingi S. 2001. Cutaneous adverse reactions to hydroxyurea in patients with sickle cell disease. Arch Dermatol 137: 467– 470. Chandley AC, Hotta Y, Stern H. 1977. Biochemical analysis of meiosis in the male mouse. I. Separation of DNA labelling of specific spermatogenic stages. Chromosoma 62: 243– 253. Charache S, Barton FB, Moore RD, Terrin ML, Steinberg MH, Dover GJ, Ballas SK, McMahon RP, Castro O, Orringer EP. 1996. Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive “switching” agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Medicine 75: 300– 326. Charache S, Dover GJ, Moyer MA, Moore JW. 1987. Hydroxyurea-induced augmentation of fetal hemoglobin production in patients with sickle cell anemia. Blood 69: 109– 116. Charache S, Terrin ML, Moore RD, Dover GJ, Bonds DR, et al. 1995. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med 332: 1317– 1322. Chaube S, Murphy ML. 1966. The effects of hydroxyurea and related compounds on the rat fetus. Cancer Res 26: 1448– 1457. Chaube S, Murphy ML. 1973. Protective effect of deoxycytidylic acid (CdMP) on hydroxyurea-induced malformations in rats. Teratology 7: 79– 87. ChemIDplus. 2004. Hydroxyurea. Available at http://chem.sis.nlm.nih.gov/chemidplus/jsp/common/ChemFull.jsp?calledFrom=lite. Chim CS, Kwong YL, Lie AK, Ma SK, Chan CC, Wong LG, Kho BC, Lee HK, Sim JP, Chan CH, Chan JC, Yeung YM, Law M, Liang R. 2005. Long-term outcome of 231 patients with essential thrombocythemia: prognostic factors for thrombosis, bleeding, myelofibrosis, and leukemia. Arch Intern Med 165: 2651– 2658. Cinkotai KI, Wood P, Donnai P, Kendra J. 1994. Pregnancy after treatment with hydroxyurea in a patient with primary thrombocythemia and a history of recurrent abortion. J Clin Pathol 47: 769– 770. Clayton DL, McMullen AW, Barnett CC. 1975. Circadian modification of drug-induced teratogenesis in rat fetuses. Chronobiologia 2: 210– 217. Coakley ME, Rawlings SJ, Brown NA. 1986. Short-chain carboxylic acids, a new class of teratogens: studies of potential biochemical mechanisms. Environ Health Perspect 70: 105– 111. Cornu P. 1994. [Long-term hematological management of cyanotic congenital heart diseases]. Arch Mal Coeur Vaiss 87: 1413– 1420. Courchesne CL, Bantle JA. 1985. Analysis of the activity of DNA, RNA, and protein synthesis inhibitors on Xenopus embryo development. Teratog Carcinog Mutagen 5: 177– 193. Dalton RN, Turner C, Dick M, Height SE, Awogbade M, Inusa B, Okpala I, O'Driscoll S, Thein SL, Rees DC. 2005. The measurement of urinary hydroxyurea in sickle cell anaemia. Br J Haematol 130: 138– 144. Daston GP, Baines D, Elmore E, Fitzgerald MP, Sharma S. 1995. Evaluation of chick embryo neural retina cell culture as a screen for developmental toxicants. Fundam Appl Toxicol 26: 203– 210. Davies SC, Gilmore A. 2003. The role of hydroxyurea in the management of sickle cell disease. Blood Rev 17: 99– 109. Dawson DA, Bantle JA. 1987. Coadministration of methylxanthines and inhibitor compounds potentiates teratogenicity in Xenopus embryos. Teratology 35: 221– 227. Dawson DA, Wilke TS. 1991. Evaluation of the frog embryo teratogenesis assay: Xenopus (FETAX) as a model system for mixture toxicity hazard assessment. Environ Toxicol Chem 10: 941– 948. Dawson DA, Wilke TS. 1992. Joint actions of developmental toxicants in Xenopus embryos: binary mixtures of DNA synthesis inhibitors. Fundam Appl Toxicol 19: 202– 206. de Montalembert M, Begue P, Bernaudin F, Thuret I, Bachir D, Micheau M. 1999. Preliminary report of a toxicity study of hydroxyurea in sickle cell disease. French Study Group on Sickle Cell Disease. Arch Dis Child 81: 437– 439. de Montalembert M, Belloy M, Bernaudin F, Gouraud F, Capdeville R, Mardini R, Philippe N, Jais JP, Bardakdjian J, Ducrocq R, Maier-Redelsperger M, Elion J, Labie D, Girot R. 1997. Three-year follow-up of hydroxyurea treatment in severely ill children with sickle cell disease. The French Study Group on Sickle Cell Disease. J Pediatr Hematol Oncol 19: 313– 318. de Montalembert M, Brousse V, Elie C, Bernaudin F, Shi J, Landais P. 2006. Long-term hydroxyurea treatment in children with sickle cell disease: tolerance and clinical outcomes. Haematologica 91: 125– 128. Dell'Isola A, Di Rosa G, Catalano D. 1997. [Essential thrombocythemia in pregnancy. A case report and general considerations]. Minerva Ginecol 49: 165– 172. Delmer A, Rio B, Bauduer F, Ajchenbaum F, Marie JP, Zittoun R. 1992. Pregnancy during myelosuppressive treatment for chronic myelogenous leukemia. Br J Haematol 82: 783– 784. DePass LR, Weaver EV. 1982. Comparison of teratogenic effects of aspirin and hydroxyurea in the Fischer 344 and Wistar strains. J Toxicol Environ Health 10: 297– 305. DeSesso JM. 1981a. Amelioration of teratogenesis. I. Modification of hydroxyurea-induced teratogenesis by the antioxidant propyl gallate. Teratology 24: 19– 35. DeSesso JM. 1981b. Comparative ultrastructural alterations in rabbit limb-buds after a teratogenic dose of either hydroxyurea or methotrexate. Teratology 23: 197– 215. DeSesso JM, Goeringer GC. 1990a. Ethoxyquin and nordihydroguaiaretic acid reduce hydroxyurea developmental toxicity. Reprod Toxicol 4: 267– 275. DeSesso JM, Goeringer GC. 1990b. The nature of the embryo-protective interaction of propyl gallate with hydroxyurea. Reprod Toxicol 4: 145– 152. DeSesso JM, Jacobson CF, Scialli AR, Goeringer GC. 2000. Hydroxylamine moiety of developmental toxicants is associated with early cell death: a structure-activity analysis. Teratology 62: 346– 355. DeSesso JM, Jordan RL. 1977. Drug-induced limb dysplasias in fetal rabbits. Teratology 15: 199– 211. Desesso JM, Scialli AR, Goeringer GC. 1994. D-mannitol, a specific hydroxyl free radical scavenger, reduces the developmental toxicity of hydroxyurea in rabbits. Teratology 49: 248– 259. Diav-Citrin O, Hunnisett L, Sher GD, Koren G. 1999. Hydroxyurea use during pregnancy: a case report in sickle cell disease and review of the literature. Am J Hematol 60: 148– 150. Dietrich AJ, Scholten R, Vink AC, Oud JL. 1983. Testicular cell suspensions of the mouse in vitro. Andrologia 15: 236– 246. Doney KC, Kraemer KG, Shepard TH. 1979. Combination chemotherapy for acute myelocytic leukemia during pregnancy: three case reports. Cancer Treat Rep 63: 369– 371. Elira Dokekias A, Okandze Elenga JP, Ndinga J, Sanogo I, Sangare A. 2005. Evaluation of clinical response by hydroxyurea in 132 patients with major sickle cell anemia]. Tunis Med 83: 32– 37. Evenson DP, Jost LK. 1993. Hydroxyurea exposure alters mouse testicular kinetics and sperm chromatin structure. Cell Prolif 26: 147– 159. Fadilah SA, Ahmad-Zailani H, Soon-Keng C, Norlaila M. 2002. Successful treatment of chronic myeloid leukemia during pregnancy with hydroxyurea. Leukemia 16: 1202– 1203. Food and Drug Administration. 1998a. Application number: 75020; review package available at [email protected] Center for Drug Evaluation and Research. Food and Drug Administration. 1998b. Application number: 75143 Approval package, available at [email protected] Center for Drug Evaluation and Research. Food and Drug Administration. 2006. [email protected] Hydroxyurea. Available at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Ferm VH. 1965. Teratogenic activity of hydroxyurea. Lancet 1: 1338– 1339. Ferm VH. 1966. Severe developmental malformations: malformations induced by urethane and hydroxyurea in the hamster. Arch Pathol 81: 174– 177. Ferster A, Tahriri P, Vermylen C, Sturbois G, Corazza F, Fondu P, Devalck C, Dresse MF, Feremans W, Hunninck K, Toppet M, Philippet P, Van Geet C, Sariban E. 2001. Five years of experience with hydroxyurea in children and young adults with sickle cell disease. Blood 97: 3628– 3632. Ferster A, Vermylen C, Cornu G, Buyse M, Corazza F, Devalck C, Fondu P, Toppet M, Sariban E. 1996. Hydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial. Blood 88: 1960– 1964. Ficsor G, Ginsberg LC. 1980. The effect of hydroxyurea and mitomycin C on sperm motility in mice. Mutat Res 70: 383– 387. Finazzi G, Harrison C. 2005. Essential thrombocythemia. Semin Hematol 42: 230– 238. Finch RA, Gardner HSJr, Bantle JA. 1995. Frog embryo teratogenesis assay-Xenopus: a nonmammalian method for developmental toxicity assessment. In: H Salem, editor. Animal test alternatives: refinement, reduction, replacement. New York: Marcel Dekker. p 297– 313. Fitzgerald JM, McCann SR. 1993. The combination of hydroxyurea and leucapheresis in the treatment of chronic myeloid leukaemia in pregnancy. Clin Lab Haematol 15: 63– 65. Fixler J, Styles L. 2002. Sickle cell disease. Pediatr Clin North Am 49: 1193– 1210. Fritz H, Hess R. 1980. Effects of hydroxyurea on postnatal growth and behaviour of rats. Agents Actions 10: 389– 393. Fung EB, Barden EM, Kawchak DA, Zemel BS, Ohene-Frempong K, Stallings VA. 2001. Effect of hydroxyurea therapy on resting energy expenditure in children with sickle cell disease. J Pediatr Hematol Oncol 23: 604– 608. Garozzo G, Disca S, Fidone C, Bonomo P. 2000. Azoospermia in a patient with sickle cell disease treated with hydroxyurea. Haematologica 85: 1216– 1218. Giavini E, Nossan N, Prati M, Vismara C. 1979. Relation of hydroxyurea embryotoxicity to the period of treatment in rats. Rend Ist Lomb Accad Sci Lett B 113: 73– 84. Gill FM, Sleeper LA, Weiner SJ, Brown AK, Bellevue R, Grover R, Pegelow CH, Vichinsky E. 1995. Clinical events in the first decade in a cohort of infants with sickle cell disease. Cooperative study of sickle cell disease. Blood 86: 776– 783. Griesshammer M, Bergmann L, Pearson T. 1998. Fertility, pregnancy and the management of myeloproliferative disorders. Bailliere Clin Haematol 11: 859– 874. Guntakatta M, Matthews EJ, Rundell JO. 1984. Development of a mouse embryo limb bud cell culture system for the estimation of chemical teratogenic potential. Teratog Carcinog Mutagen 4: 349– 364. Gupta C, Yaffe SJ. 1982. Phenobarbital-induced alterations in the sexual differentiation of the female rat: reversal by hydroxyurea and cycloheximide. Pediatr Pharmacol 2: 85– 91. Gwilt PR, Tracewell WG. 1998. Pharmacokinetics and pharmacodynamics of hydroxyurea. Clin Pharmacokinet 34: 347– 358. Halsey C, Roberts IA. 2003. The role of hydroxyurea in sickle cell disease. Br J Haematol 120: 177– 186. Hanft VN, Fruchtman SR, Pickens CV, Rosse WF, Howard TA, Ware RE. 2000. Acquired DNA mutations associated with in vivo hydroxyurea exposure. Blood 95: 3589– 3593. Hankins JS, Ware RE, Rogers ZR, Wynn LW, Lane PA, Scott JP, Wang WC. 2005. Long-term hydroxyurea therapy for infants with sickle cell anemia: the HUSOFT extension study. Blood 106: 2269– 2275. Hansen DK, Grafton TF, Cross DR, James SJ. 1995. Partial attenuation of hydroxyurea-induced embryotoxicity by deoxyribonucleotides in mouse and rat embryos treated in vitro. Toxicol In Vitro 9: 11– 19. Harrod VL, Howard TA, Zimmerman SA, Dertinger SD, Ware RE. 2007. Quantitative analysis of Howell-Jolly bodies in children with sickle cell disease. Exp Hematol. 35: 179– 183. Herken R. 1980. Cell cycle phase specificity of hydroxyurea and its effects on the cell kinetics in embryonic spinal cord. Teratology 21: 9– 14. Herken R. 1984. The influence of deoxycytidine monophosphate (dCMP) on the cytotoxicity of hydroxyurea in the embryonic spinal cord of the mouse. Teratology 30: 83– 90. Herken R. 1985. Ultrastructural changes in the neural tube of 10-day-old mouse embryos exposed to colchicine and hydroxyurea. Teratology 31: 345– 352. Herken R, Gehler M, Merker HJ. 1982. The influence of colchicine on the cytotoxic effect of hydroxyurea in the embryonic spinal cord of the mouse. Eur J Cell Biol 28: 54– 59. Herken R, Merker HJ, Krowke R. 1978. Investigation of the effect of hydroxyurea on the cell cycle and the development of necrosis in the embryonic CNS in mice. Teratology 18: 103– 118. Hoppe C, Vichinsky E, Quirolo K, van Warmerdam J, Allen K, Styles L. 2000. Use of hydroxyurea in children ages 2 to 5 years with sickle cell disease. J Pediatr Hematol Oncol 22: 330– 334. Hurley TJ, McKinnell JV, Irani MS. 2005. Hematologic malignancies in pregnancy. Obstet Gynecol Clin North Am 32: 595– 614. IARC. 2000. Monographs on the evaluation of the carcinogenic risk of chemicals to man. Hydroxyurea. 76. Iwama M, Sakamoto Y, Honda A, Mori Y. 1983. Limb deformity induced in chick embryo by hydroxyurea. J Pharmacobiodyn 6: 836– 843. Jackson N, Shukri A, Ali K. 1993. Hydroxyurea treatment for chronic myeloid leukaemia during pregnancy. Br J Haematol 85: 203– 204. Jayabose S, Tugal O, Sandoval C, Patel P, Puder D, Lin T, Visintainer P. 1996. Clinical and hematologic effects of hydroxyurea in children with sickle cell anemia. J Pediatr 129: 559– 565. Kaplay M, Prabhakar V, Rao KS. 1983. Hydroxyurea inhibits thymidine kinase activity in developing rat cerebellum. Biochem Int 6: 473– 480. Karimi M, Darzi H, Yavarian M. 2005. Hematologic and clinical responses of thalassemia intermedia patients to hydroxyurea during 6 years of therapy in Iran. J Pediatr Hematol Oncol 27: 380– 385. Kavlock RJ, Short RDJ, Chernoff N. 1987. Further evaluation of an in-vivo teratology screen. Teratog Carcinog Mutagen 7: 7– 16. Kemppainen BW, Terse P, Zurovac O, Stringfellow D. 1996. Preliminary evaluation of in vitro prescreen assays for developmental toxicants based on cultured murine preimplantation embryos and a cell line developed from a bovine preimplantation embryo. Toxicol In Vitro 10: 323– 330. Khayat AS, Antunes LM, Guimaraes AC, Bahia MO, Lemos JA, Cabral IR, Lima PD, Amorim MI, Cardoso PC, Smith MA, Santos RA, Burbano RR. 2006. Cytotoxic and genotoxic monitoring of sickle cell anaemia patients treated with hydroxyurea. Clin Exp Med 6: 33– 37. Khera KS. 1979. A teratogenicity study on hydroxyurea and diphenylhydantoin in cats. Teratology 20: 447– 452. Khera KS, Whalen C. 1988. Detection of neuroteratogens with an in-vitro cytotoxicity assay
Referência(s)