Establishment and assessment of a new human embryonic stem cell-based biomarker assay for developmental toxicity screening

Birth Defects Research Part B - Developmental and Reproductive Toxicology

Volumn 98, Issue 4, 2013, Pages 343-363

  Palmer, Jessica A ^a   Smith, Alan M ^a   Egnash, Laura A ^a   Conard, Kevin R ^a   West, Paul R ^a   Burrier, Robert E ^a   Donley, Elizabeth L R ^a   Kirchner, Fred R ^a  

^a Stemina Biomarker Discovery Inc   (United States)

Author keywords

Biomarker identification; Human embryonic stem cells; In vitro developmental toxicity screen; In vitro toxicology; Mechanisms of teratogenesis; Metabolomics; Retinoic acid; Valproic acid

Indexed keywords

ACICLOVIR; AMOXICILLIN; ASCORBIC ACID; BIOLOGICAL MARKER; BUSULFAN; CAFFEINE; CARBAMAZEPINE; CYSTINE; CYTARABINE; DIPHENHYDRAMINE; DOXYLAMINE; FLUOROURACIL; FOLIC ACID ANTAGONIST; HYDROXYUREA; ISONIAZID; ISOTRETINOIN; LEVOTHYROXINE; METHOTREXATE; ORNITHINE; PARACETAMOL; PENICILLIN G; PHENYTOIN; RETINOIC ACID; RETINOL; SACCHARIN; THALIDOMIDE; THIAMINE; UNINDEXED DRUG; VALPROIC ACID; WARFARIN;

ACCURACY; ARTICLE; BIOASSAY; CELL CULTURE; CELL METABOLISM; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; CYTOTOXICITY; DEVELOPMENTAL SCREENING; DEVELOPMENTAL TOXICITY; DOSE RESPONSE; EMBRYONIC STEM CELL; EXPOSURE; HUMAN; HUMAN CELL; IN VITRO STUDY; METABOLITE; METABOLOMICS; PREDICTION; PREGNANCY; PRIORITY JOURNAL; SENSITIVITY AND SPECIFICITY; TERATOGENICITY;

ANIMALIA;

BIOMARKER IDENTIFICATION; HUMAN EMBRYONIC STEM CELLS; IN VITRO DEVELOPMENTAL TOXICITY SCREEN; IN VITRO TOXICOLOGY; MECHANISMS OF TERATOGENESIS; METABOLOMICS; RETINOIC ACID; VALPROIC ACID;

BIOLOGICAL ASSAY; BIOLOGICAL MARKERS; CELL LINE; CELL SURVIVAL; EMBRYONIC DEVELOPMENT; EMBRYONIC STEM CELLS; FEMALE; HUMANS; METABOLOMICS; MODELS, BIOLOGICAL; PREGNANCY; TERATOGENS; TOXICITY TESTS;

EID: 84885857859     PISSN: 15429733     EISSN: 15429741     Source Type: Journal    
DOI: 10.1002/bdrb.21078     Document Type: Article

References (96)

1. AbbVie. 2013. Depacon [product information]. North Chicago, IL.
2. ACToR database. 2013. Web site. Available at: http://actor.epa.gov/actor/faces/ACToRHome.jsp. Accessed July 2013.
3. Andrx Labs. 2012. Altoprev [product information]. Fort Lauderdale, FL.
4. Baxter Healthcare. 2012. Penicillin G potassium injection [product information]. Deerfield, IL.
5. Bedford Laboratories. 2001. Thiotepa [product information]. Bedford, OH.
6. Bhattacharya S, Zhang Q, Carmichael PL, Boekelheide K, Andersen ME. 2011. Toxicity testing in the 21 century: defining new risk assessment approaches based on perturbation of intracellular toxicity pathways. PLoS One 6:e20887.
7. Blomhoff R, Beckman-Sundh U, Brot C, Solvoll K, Steingrimsdottir L, Carlsen MH. 2003. Health risks related to high intake of preformed retinol (vitamin A) in the Nordic countries. Copenhagen: Nordic Council of Ministers.
8. Brannen KC, Panzica-Kelly JM, Danberry TL, Augustine-Rauch KA. 2010. Development of a zebrafish embryo teratogenicity assay and quantitative prediction model. Birth Defects Res B Dev Reprod Toxicol 89:66-77.
9. Briggs GG, Freeman RK, Yaffe SJ. 2011. Drugs in pregnancy and lactation. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins.
10. Brown NA. 2002. Selection of test chemicals for the ECVAM international validation study on in vitro embryotoxicity tests. European Centre for the Validation of Alternative Methods. Altern Lab Anim 30:177-198.
11. Caffeine Pharmacology. n.d. Medscape web site. Available at http://reference.medscape.com/drug/cafcit-nodoz-caffeine-342995#10. Accessed August 2011.
12. Chan LY, Lau TK. 2006. Effect of rosiglitazone on embryonic growth and morphology: a study using a whole rat embryo culture model. Fertil Steril 86:490-492.
13. Clark RL. 2009. Embryotoxicity of the artemisinin antimalarials and potential consequences for use in women in the first trimester. Reprod Toxicol 28:285-296.
14. Cole PD, Drachtman RA, Smith AK, Cate S, Larson RA, Hawkins DS, Holcenberg J, Kelly K, Kamen BA. 2005. Phase II trial of oral aminopterin for adults and children with refractory acute leukemia. Clin Cancer Res 11:8089-8096.
15. Daston GP, Knudsen TB. 2010. Fundamental concepts, current regulatory design and interpretation. In: Knudsen TB, Daston GP, editors. Comprehensive toxicology. 2nd ed. New York: Elsevier. Vol. 12, p 3-9.
16. Daston GP, Chapin RE, Scialli AR, Piersma AH, Carney EW, Rogers JM, Friedman JM. 2010. A different approach to validating screening assays for developmental toxicity. Birth Defects Res B Dev Reprod Toxicol 89:526-530.
17. Dr Reddy's Laboratories. 2011. Amoxil [product information]. Bridgewater, NJ.
18. Drewe J, Delco F, Kissel T, Beglinger C. 2003. Effect of intravenous infusion of thiamine on the disposition kinetics of thiamine and its pyrophosphate. J Clin Pharm Ther 28:47-51.
19. Ebert AD, Svendsen CN. 2010. Human stem cells and drug screening: opportunities and challenges. Nat Rev Drug Discov 9:367-372.
20. Genschow E, Spielmann H, Scholz G, Pohl I, Seiler A, Clemann N, Bremer S, Becker K. 2004. Validation of the embryonic stem cell test in the international ECVAM validation study on three in vitro embryotoxicity tests. Altern Lab Anim 32:209-244.
21. Gilead Sciences. 2000. Vistide [product information]. Foster City, CA.
22. Gilead Sciences. 2012. Hepsera [product information]. Foster City, CA.
23. GlaxoSmithKline. 2005. Agenerase [product information]. Research Triangle Park, NC.
24. GlaxoSmithKline. 2011. Avandia [product information]. Research Triangle Park, NC.
25. GlaxoSmithKline. 2012. Ziagen [product information]. Research Triangle Park, NC.
26. GlaxoSmithKline. 2013. Tykerb [product information]. Research Triangle Park, NC.
27. Gustafson AL, Stedman DB, Ball J, Hillegass JM, Flood A, Zhang CX, Panzica-Kelly J, Cao J, Coburn A, Enright BP, Tornesi MB, Hetheridge M, Augustine-Rauch KA. 2012. Inter-laboratory assessment of a harmonized zebrafish developmental toxicology assay-progress report on phase I. Reprod Toxicol 33:155-164.
28. Hansen DK. 1995. Folates in reproduction: in vitro studies. Teratology 51:12A.
29. Hansen DK, Grafton TF, Dial SL. 1993. Effect of dietary supplementation with folic acid on valproate-induced neural tube defects. Teratology 47:420.
30. Hansen JM. 2006. Oxidative stress as a mechanism of teratogenesis. Birth Defects Res C Embryo Today 78:293-307.
31. Hartmann S, Brørs O, Bock J, Blomhoff R, Bausch J, Wiegand UW, Hartmann D, Hornig DH. 2005. Exposure to retinyl esters, retinol, and retinoic acids in non-pregnant women following increasing single and repeated oral doses of vitamin A. Ann Nutr Metab 49:155-164.
32. Herrmann K. 1995. Teratogenic effects of retinoic acid and related substances on the early development of the zebrafish (Brachydanio rerio) as assessed by a novel scoring system. Toxicol In Vitro 9:267-283.
33. Hilbert J, Radwanski E, Weglein R, Luc V, Perentesis G, Symchowicz S, Zampaglione N. 1987. Pharmacokinetics and dose proportionality of loratadine. J Clin Pharmacol 27:694-698.
34. Hoyert DL, Mathews TJ, Menacker F, Strobino DM, Guyer B. 2006. Annual summary of vital statistics: 2004. Pediatrics 117:168-183.
35. Isoniazid (Systemic). n.d. Drugs.com Web site. Available at: http://www.drugs.com/mmx/isoniazid.html. Updated June 30, 2000. Accessed August 2011.
36. Jelovsek FR, Mattison DR, Chen JJ. 1989. Prediction of risk for human developmental toxicity: how important are animal studies for hazard identification? Obset Gynecol 74:624-636.
37. Kalhan SC, Bier DM. 2008. Protein and amino acid metabolism in the human newborn. Annu Rev Nutr 28:389-410.
38. Karim A, Tolbert D, Cao C. 2006. Disposition kinetics and tolerance of escalating single doses of ramelteon, a high-affinity MT1 and MT2 melatonin receptor agonist indicated for treatment of insomnia. J Clin Pharmacol 46:140-148.
39. Kleinstreuer NC, Smith AM, West PR, Conard KR, Fontaine BR, Weir-Hauptman AM, Palmer JA, Knudsen TB, Dix DJ, Donley EL, Cezar GG. 2011. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics. Toxicol Appl Pharmacol 257:111-121.
40. Klug S, Lewandowski C, Blankenburg G, Merker HJ, Neubert D. 1985. Effect of acyclovir on mammalian embryonic development in culture. Arch Toxicol 58:89-96.
41. Klug S, Creech Kraft J, Wildi E, Merker HJ, Persaud TV, Nau H, Neubert D. 1989. Influence of 13-cis and all-trans retinoic acid on rat embryonic development in vitro: correlation with isomerisation and drug transfer to the embryo. Arch Toxicol 63:185-192.
42. Kovacic P, Somanathan R. 2006. Mechanism of teratogenesis: electron transfer, reactive oxygen species, and antioxidants. Birth Defects Res C Embryo Today 78:308-325.
43. Lankas GR, Cukierski MA, Wise LD. 2004. The role of maternal toxicity in lovastatin-induced developmental toxicity. Birth Defects Res B Dev Reprod Toxicol 71:111-123.
44. Leucuţa A, Vlase L, Farcǎu D, Nanulescu M. 2004. Pharmacokinetic interaction study between ranitidine and metoclopramide. Rom J Gastroenterol 13:211-214.
45. Liebelt EL, Balk SJ, Faber W, Fisher JW, Hughes CL, Lanzkron SM, Lewis KM, Marchetti F, Mehendale HM, Rogers JM, Shad AT, Skalko RG, Stanek EJ. 2007. NTP-CERHR expert panel report on the reproductive and developmental toxicity of hydroxyurea. Birth Defects Res B Dev Reprod Toxicol 80:259-366.
46. Louisse J, Gönen S, Rietjens IM, Verwei M. 2011. Relative developmental toxicity potencies of retinoids in the embryonic stem cell test compared with their relative potencies in in vivo and two other in vitro assays for developmental toxicity. Toxicol Lett 203:1-8.
47. Luna BG, Scavone JM, Greenblatt DJ. 1989. Doxylamine and diphenhydramine pharmacokinetics in women on low-dose estrogen oral contraceptives. J Clin Pharmacol 29:257-260.
48. Madureira TV, Cruzeiro C, Rocha MJ, Rocha E. 2011. The toxicity potential of pharmaceuticals found in the Douro River estuary (Portugal)-experimental assessment using a zebrafish embryo test. Environ Toxicol Pharmacol 32:212-217.
49. Mahmood I, Chamberlin N. 1998. A limited sampling method for the estimation of AUC and Cmax of carbamazepine and carbamazepine epoxide following a single and multiple dose of a sustained-release product. Br J Clin Pharmacol 45:241-246.
50. Mao Y, Gurr JA, Hickok NJ. 1993. Retinoic acid regulates ornithine decarboxylase gene expression at the transcriptional level. Biochem J 295:641-644.
51. Marx-Stoelting P, Adriaens E, Ahr HJ, Bremer S, Garthoff B, Gelbke HP, Piersma A, Pellizzer C, Reuter U, Rogiers V, Schenk B, Schwengberg S, Seiler A, Spielmann H, Steemans M, Stedman DB, Vanparys P, Vericat JA, Verwei M, van der Water F, Weimer M, Schwarz M. 2009. A review of the implementation of the embryonic stem cell test (EST). The report and recommendations of an ECVAM/ReProTect Workshop. Altern Lab Anim 37:313-328.
52. Mayne Pharma. n.d. Aquasol A [product information]. Paramus, NJ.
53. McGrath P, Li CQ. 2008. Zebrafish: a predictive model for assessing drug-induced toxicity. Drug Discov Today 13:394-401.
54. McNeil Consumer Healthcare. 2010. Tylenol [Product Information]. Fort Washington, PA.
55. Merck. 2004. Cuprimine [product information]. Whitehouse Station, NJ.
56. Merck. 2013. Januvia [product information]. Whitehouse Station, NJ.
57. Miller RS, Li Q, Cantilena LR, Leary KJ, Saviolakis GA, Melendez V, Smith B, Weina PJ. 2012. Pharmacokinetic profiles of artesunate following multiple intravenous doses of 2, 4, and 8 mg/kg in healthy volunteers: phase 1b study. Malar J 11:255.
58. Muindi JR, Frankel SR, Huselton C, DeGrazia F, Garland WA, Young CW, Warrell RP Jr. 1992. Clinical pharmacology of oral all-trans retinoic acid in patients with acute promyelocytic leukemia. Cancer Res 52:2138-2142.
59. National Research Council (NRC). 2000. Scientific frontiers in developmental toxicology and risk assessment. Washington, DC: The National Academies Press.
60. National Research Council (NRC). 2007. Toxicity testing in the 21st century. A vision and a strategy. Washington, DC: The National Academies Press.
61. Novartis Pharmaceuticals. 2010. Comtan [product information]. East Hanover, NJ.
62. Novartis Sverige AB. 2011. Everolimus [product information]. Täby, Sweden.
63. Oman M, Lundqvist S, Gustavsson B, Hafström LO, Naredi P. 2005. Phase I/II trial of intraperitoneal 5-Fluorouracil with and without intravenous Vasopressin in non-resectable pancreas cancer. Cancer Chemother Pharmacol 56:603-609.
64. Otsuka America Pharmaceutical. 2011. Busulfex [product information]. Rockville, MD.
65. Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, Wesley RA, Levine M. 2004. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med 140:533-537.
66. Palma-Aguirre JA, Absalón-Reyes JA, Novoa-Heckel G, de Lago A, Oliva I, Rodríguez Z, González-de la Parra M, Burke-Fraga V, Namur S. 2007. Bioavailability of two oral suspension and two oral tablet formulations of acyclovir 400 mg: two single-dose, open-label, randomized, two-period crossover comparisons in healthy Mexican adult subjects. Clin Ther 29:1146-1152.
67. Paquette JA, Kumpf SW, Streck RD, Thomson JJ, Chapin RE, Stedman DB. 2008. Assessment of the embryonic stem cell test and application and use in the pharmaceutical industry. Birth Defects Res B Dev Reprod Toxicol 83:104-111.
68. Pegg A. 2009. Mammalian polyamine metabolism and function. IUBMB Life 61:880-894.
69. Pfizer. 2012. Dilantin [product information]. New York, NY.
70. Piersma AH, Attenon P, Bechter R, Govers MJAP, Krafft N, Schmid BP, Stadler J, Verhoef A, Verseil C. 1995. Interlaboratory evaluation of embryotoxicity in the postimplantation rat embryo culture. Reprod Toxicol 9:275-280.
71. Ritchie HE, Brown-Woodman PD, Korabelnikoff A. 2003. Effect of co-administration of retinoids on rat embryo development in vitro. Birth Defects Res A Clin Mol Teratol 67:444-451.
72. Ritz C, Streibig JC. 2005. Bioassay analysis using R. J Statistical Software 12:1-22.
73. Robinson JF, van Beelen VA, Verhoef A, Renkens MF, Luijten M, van Herwijnen MH, Westerman A, Pennings JL, Piersma AH. 2010. Embryotoxicant-specific transcriptomic responses in rat postimplantation whole-embryo culture. Toxicol Sci 118:675-685.
74. Roche Laboratories. 2010. Accutane [product information]. Nutley, NJ.
75. Scott CW, Peters MF, Dragan YP. 2013. Human induced pluripotent stem cells and their use in drug discovery for toxicity testing. Toxicol Lett 219:49-58.
76. Selderslaghs IW, Blust R, Witters HE. 2012. Feasibility study of the zebrafish assay as an alternative method to screen for developmental toxicity and embryotoxicity using a training set of 27 compounds. Reprod Toxicol 33:142-154.
77. Shepard TH, Lemire RJ. 2007. Catalog of teratogenic agents. 12th ed. Baltimore, MD: The Johns Hopkins University Press.
78. Shoda H, Inokuma S, Yajima N, Tanaka Y, Oobayashi T, Setoguchi K. 2007. Higher maximal serum concentration of methotrexate predicts the incidence of adverse reactions in Japanese rheumatoid arthritis patients. Mod Rheumatol 17:311-316.
79. Shuren J. 2008. Content and format of labeling for human prescription drug and biological products; requirements for pregnancy and lactation labeling. Fed Regist 73:30831-30868.
80. Smith CA, Want EJ, O'Maille G, Abagyan R, Siuzdak G. 2006. XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification. Anal Chem 78:779-787.
81. Stark KL, Lee QP, Namkung MJ, Harris C, Juchau MR. 1990. Dysmorphogenesis elicited by microinjected acetaminophen analogs and metabolites in rat embryos cultured in vitro. J Pharmacol Exp Ther 255:74-82.
82. Tandon S, Jyoti S. 2012. Embryonic stem cells: an alternative approach to developmental toxicity testing. J Pharm Bioallied Sci 4:96-100.
83. Teratogen Information System (TERIS). 2013. Web site. Available at: http://depts.washington.edu/terisweb/teris/. Accessed July 2013.
84. Teratology Society. 1987. Teratology Society position paper: recommendations for vitamin A use during pregnancy. Teratology 35:269-275.
85. Thalidomide Pharmacology. n.d. Medscape web site. Available at: http://reference.medscape.com/drug/thalomid-thalidomide-343211#10. Accessed August 2011.
86. Theunissen PT, Piersma AH. 2012. Innovative approaches in the embryonic stem cell test (EST). Front Biosci 17:1965-1975.
87. Thomson J, Johnson K, Chapin R, Stedman D, Kumpf S, Ozolinš TR. 2011. Not a walk in the park: the ECVAM whole embryo culture model challenged with pharmaceuticals and attempted improvements with random forest design. Birth Defects Res B Dev Reprod Toxicol 92:111-121.
88. Ubeda N, Reyes L, González-Medina A, Alonso-Aperte E, Varela-Moreiras G. 2011. Physiologic changes in homocysteine metabolism in pregnancy: a longitudinal study in Spain. Nutrition 27:925-930.
89. Vaisman M, Spina LD, Eksterman LF, dos Santos MJ, Lima JS, Volpato NM, da Silva RL, de Brito AP, Noël F. 2001. Comparative bioavailability of two oral l-thyroxine formulations after multiple dose administration in patients with hypothyroidism and its relation with therapeutic endpoints and dissolution profiles. Arzneimittelforschung 51:246-252.
90. van Giersbergen PL, Treiber A, Schneiter R, Dietrich H, Dingemanse J. 2007. Inhibitory and inductive effects of rifampin on the pharmacokinetics of bosentan in healthy subjects. Clin Pharmacol Ther 81:414-419.
91. Warner Chilcott. 2013. Sarafem [product information]. Rockaway, NJ.
92. Weigt S, Huebler N, Strecker R, Braunbeck T, Broschard TH. 2011. Zebrafish (Danio rerio) embryos as a model for testing proteratogens. Toxicology 281:25-36.
93. Weinstein HJ, Griffin TW, Feeney J, Cohen HJ, Propper RD, Sallan SE. 1982. Pharmacokinetics of continuous intravenous and subcutaneous infusions of cytosine arabinoside. Blood 59:1351-1353.
94. Welle-Watne A, Wiik I, Waaler T. 1980. Bioavailability of warfarin from three tablet preparations. Medd Norsk Farm Selsk 42:103-114.
95. West PR, Weir AM, Smith AM, Donley EL, Cezar GG. 2010. Predicting human developmental toxicity of pharmaceuticals using human embryonic stem cells and metabolomics. Toxicol Appl Pharmacol 247:18-27.
96. Zhang C, Cao J, Kenyon JR, Panzica-Kelly JM, Gong L, Augustine-Rauch K. 2012. Development of a streamlined rat whole embryo culture assay for classifying teratogenic potential of pharmaceutical compounds. Toxicol Sci 127:535-546.