Predictive value of in vitro safety studies

Current Opinion in Chemical Biology

Volumn 10, Issue 4, 2006, Pages 362-366

  Suter, Willi ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CANCER; CARCINOGENESIS; DRUG INDUSTRY; DRUG METABOLISM; DRUG SAFETY; GENETIC TOXICOLOGY; HEART ELECTROPHYSIOLOGY; HEART REPOLARIZATION; HUMAN; LIVER TOXICITY; MEDICAL TECHNOLOGY; NONHUMAN; PHARMACEUTICAL CARE; PREDICTION; QT PROLONGATION; REVIEW; RISK ASSESSMENT; SAFETY; SENSITIVITY AND SPECIFICITY; STEM CELL;

ANIMALS; DNA DAMAGE; DRUG EVALUATION, PRECLINICAL; ELECTROPHYSIOLOGY; HEART; LIVER; PREDICTIVE VALUE OF TESTS; TOXICITY TESTS;

EID: 33746104810     PISSN: 13675931     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cbpa.2006.06.023     Document Type: Review

References (52)

1. Snodin D.J. An EU perspective on the use of in vitro methods in regulatory pharmaceutical toxicology. Toxicol Lett 127 (2002) 161-168
2. Anon: ICH S7B: The non-clinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals. The ICH Steering Committee, 2005: http://www.ich.org/cache/compo/502-272-1.html#S7B.
3. Louekari K. Status and prospect of in vitro tests in risk assessment. Altern Lab Anim 32 (2004) 431-435
4. Gubbels-van Hal W.M.L.G., Blaauboer B.J., Barentsen H.M., Hoitink M.A., Meerts I.A.T.M., and van der Hoeven J.C.M. An alternative approach for the safety evaluation of new and existing chemicals, an exercise in integrated testing. Regul Toxicol Pharmacol 42 (2005) 284-295
5. Bernauer U., Oberemm A., Madle S., and Gundert-Remy U. The use of in vitro data in risk assessment. Basic Clin Pharmacol Toxicol 96 (2005) 176-181
6. Indans I. The use and interpretation of in vitro data in regulatory toxicology: cosmetics, toiletries and household products. Toxicol Lett 127 (2002) 177-182
7. Kirkland D.J., Henderson L., Marzin D., Mueller L., Parry J.M., Speit G., Tweats D.J., and Williams G.M. Testing strategies in mutagenicity and genetic toxicology: an appraisal of the guidelines of the European scientific committee for cosmetics and non-food products for the evaluation of hair dyes. Mutat Res 588 (2005) 88-105
8. Kirkland D., Aardema M., Henderson L., and Muller L. Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens I. sensitivity, specificity and relative predicitivity. Mutat Res 584 (2005) 1-256. The most extensive critical evaluation of the predicitivity of in vitro genotoxicity assays ever published. The strength and shortcomings of regulatory genotoxicity testing are analyzed in detail and potential actions for improvements are discussed.
9. Brambilla G., and Martelli A. Failure of the standard battery of short-term tests in detecting some rodent and human genotoxic carcinogens. Toxicology 196 (2004) 1-19
10. Lazarova M., Labaj J., Eckel P., and Slamenova D. Comparative evaluation of DNA damage by genotoxicants in primary rat cells applying the comet assay. Toxicol Lett 164 (2006) 54-62
11. ® as a tool for the comet assay. Mutat Res 519 (2002) 163-170
12. Bernauer U., Glatt H., Heinrich-Hirsch B., Liu Y., Muckel E., Vieth B., and Gundert-Remy U. Heterologous expression of mouse cytochrome P450 2e1 in V79 cells: construction and characterization of the cell line and comparison with V79 cell lines stably expressing rat P450 2E1 and human P450 2E1. Altern Lab Anim 31 (2003) 21-30
13. Knasmuller S., Mersch-Sundermann V., Kevekordes S., Darroudi F., Huber W.W., Hoelzl C., Bichler J., and Majer B.J. Use of human-derived liver cell lines for the detection of environmental and dietary genotoxicants; current state of knowledge. Toxicology 198 (2004) 315-328
14. Ohno K., Tanaka-Azumo Y., Yoneda Y., and Yamada T. Genotoxicity test system based on p53R2 gene expression in human cells. Examination with 80 chemicals. Mutat Res 588 (2005) 47-57
15. Speit G., and Hartmann A. The comet assay: a sensitive genotoxicity test for the detection of DNA damage. In: Keohavong P., and Grant S.G. (Eds). Molecular toxicology protocols (2005), Humana Press 85-95
16. Zhang H., Borman H.D., and Myhr B.C. Enhancement of the morphological transformation of syrian hamster embryo (SHE) cells by reducing incubation time of the target cells. Mutat Res 548 (2004) 1-7
17. Engelhardt G., Schwind K.R., and Mussler B. The testing of chemicals in the syrian hamster embryo (SHE) cell transformation assay for assessment of carcinogenic potential. Toxicol In Vitro 18 (2004) 213-218
18. Aubrecht J., and Caba E. Gene expression profile analysis:an emerging approach to investigate mechanisms of genotoxicity. Pharmacogenomics 6 (2005) 419-428
19. Hu T., Gibson D.P., Carr G.J., Torontali S.M., Tiesman J.P., Chaney J.G., and Aardema M. J. Identification of a gene expression profile that discriminates indirect-acting genotoxins from direct-acting genotoxins. Mutat Res 549 (2004) 5-27
20. Amundson S.A., Do K.T., Vinikor L., Koch-Paiz C.A., Bittner M.L., Trent J.M., Meltzer P., and Fornace Jr. J. Stress-specific signatures: expression profiling of p53 wild-type and -null human cells. Oncogene 24 (2005) 4572-4579
21. Bass A.S., Tomaselli G., Bullingham III R., and Kinter L.B. Drug effects on ventricular repolarization: a critical evaluation of the strengths and weaknesses of current methodologies and regulatory practices. J Pharmacol Toxicol Methods 52 (2005) 12-21
22. Shah R.R. Drugs, QT interval prolongation and ICH E14. The need to get it right. Drug Saf 28 (2005) 115-125
23. Redfern W.S., Carlsson L., Davis A.S., Lynch W.G., MacKenzie I., Palethorpe S., Siegl P.K.S., Strang I., Sullivan A.T., Wallis R., et al. Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc Res 58 (2003) 32-45
24. Lawrence C.L., Pollard C.E., Hammond T.G., and Valentin J.-P. Nonclinical proarrhythmia models: predicting torsade de pointes. J Pharmacol Toxicol Methods 52 (2005) 46-59. Three in vitro and three in vivo proarrhythmia models are discussed. The predictivity of the methods for QT interval prolongation and induction of torsade de pointe is described. The authors conclude that the data from proarrhythmia models and QT-related assays should be combined to achieve better predictions for the induction of torsade de pointe in humans.
25. Valentin J.-P., Hoffmann P., De Clerck F., Hammond T.G., and Hondeghem L. Review of the predictive value of the Langendorff heart model (Screenit system) in assessing the proarrhythmic potential of drugs. J Pharmacol Toxicol Methods 49 (2004) 171-181
26. Shah R.R., and Hondeghem L.M. Refining detection of drug induced proarrhythmia: QT interval and TRIaD. Heart Rhythm 2 (2005) 758-772
27. Hondeghem L.M., and Hoffmann P. Blinded test in isolated female rabbit heart reliably identifies action potential duration prolongation and proarrhythmic drugs: importance of triangulation, reverse use dependence, and instability. J Cardiovasc Pharmacol 41 (2003) 14-24
28. Hondeghem L.M., Lu H.R., Van Rossem K., and De Clerck F. Detection of proarrhythmia in the female rabbit heart: blinded validation. J Cardiovasc Electrophysiol 14 (2003) 287-294
29. Di Diego J.M., Belardinell L., and Antzelevitch C. Cisapride-induced transmural dispersion of repolarization and torsade de pointe in the canine left ventricular wedge preparation during epicardial stimulation. Circulation 108 (2003) 1027-1033
30. Extramiana F., and Antzelevitch C. Amplified transmural dispersion of repolarization as the basis for arrhythmiogenesis in a canine ventricular-wedge model of short QT syndrome. Circulation 110 (2004) 3661-3666
31. Antzelevitch C. Modulation of transmural repolarization. Ann N Y Acad Sci 1047 (2005) 314-323
32. Bottino D., Penland R.C., Stamps A., Traebert M., Dumotier B., Georgieva A., Helmlinger G., and Lett G.S. Preclinical cardiac safety assessment of pharmaceutical compounds using an integrated system-based computer model in the heart. Prog Biophys Mol Biol 90 (2006) 414-443. Not an easy reading for a biologist, but it shows how the mathematical modeling of biological data can supplement the biological data set. It elegantly demonstrates that cardiac ion channel data can be used to model cardiac function and predict drug toxicity at the organ level.
33. Xu J.J., Diaz D., and O'Brien P.J. Applications of cytotoxicity assays and prelethal mechanistic assays for assessment of human hepatotoxicity potential. Chem Biol Interact 150 (2004) 115-128. A detailed presentation of in vitro approaches to study liver toxicity caused by various mechanisms such as cholestasis and mitochondrial toxicity. It shows that in vitro investigations can provide much more detailed information than just a measurement of cytotoxicity.
34. Farkas D., and Tannenbaum S.R. In vitro methods to study chemically-induced hepatotoxicity: a literature review. Curr Drug Metab 6 (2005) 111-125
35. O'Brien P.J.O., Chan K., and Silber P.M. Human and animal hepatocytes in vitro with extrapolation in vivo. Chem Biol Interact 150 (2004) 97-114
36. Hengstler J.G., Utesch D., Steinberg P., Platt K.L., Diener B., Ringel M., Swales N., Fischer T., Biefang K., Gerl M., et al. Cryopreserved primary hepatocytes as a constantly available in vitro model for the evaluation of human and animal drug metabolism and enzyme induction. Drug Metab Rev 32 (2000) 81-118
37. Li A.P., Lu C., Brent J.A., Pham C., Fackett A., Ruegg C.E., and Silber P.M. Cryopreserved human hepatocytes: characterization of drug metabolizing enzymes activities and application in higher throughput screening assays for hepatotoxicity, metabolic stability, and drug-drug interaction potential. Chem Biol Interact 121 (1999) 17-35
38. Kikkawa R., Yamamoto T., Fukushima T., Yamada H., and Hori I. Investigation of a hepatotoxicity screening system in primary cell cultures -"what biomarkers would need to be addressed to estimate toxicity in conventional and new approaches?". J Toxicol Sci 30 (2005) 61-72
39. Boess F., Kamber M., Romer S., Gasser R., Muller D., Albertini S., and Suter L. Gene expression in two hepatic cell lines, cultured primary hepatocytes, and liver slices compared to the in vivo liver gene expression in rats: possible implications for toxicogenomics use of in vitro systems. Toxicol Sci 73 (2003) 386-402
40. Orr M.S., Higgs B.W., Johnson K.R., and Mendrick D.L. Concordance of toxicogenomic predictions and mechanistic analysis for compounds tested in both rat liver and primary rat hepatocytes. Toxicologist 78 1-S (2004) 134
41. Miret S., De Groene E.M., and Klaffke W. Comparison of in vitro assays of cellular toxicity in the human hepatic cell line HepG2. J Biomol Screen 11 (2006) 184-193
42. Dambach D.M., Andrews B.A., and Moulin F. New technologies and screening strategies for hepatotoxicity: use of in vitro models. Toxicol Pathol 33 (2005) 17-26
43. O'Brien P.J.O., and Siraki A.G. Accelerated cytotoxicity mechanism screening using drug metabolising enzyme modulators. Curr Drug Metab 6 (2005) 101-109
44. Combes R.D. Assessing risk to humans from chemical exposure by using non-animal test data. Toxicol In Vitro 19 (2005) 921-924
45. Wobus A.M., and Boheler K.R. Embryonic stem cells: prospects for developmental biology and cell therapy. Physiol Rev 85 (2005) 635-678
46. Davila J.C., Cezar G.G., Thiede M., Strom S., Miki T., and Trosko J. Use and application of stem cells in toxicology. Toxicol Sci 79 (2004) 214-223. A concise review of the applications of adult and embryonic stem cells in toxicology that focuses on the three areas of in vitro testing discussed in the present review. The authors show that the use of stem cells is an emerging and promising field in toxicology, although no breakthroughs have been achieved so far.
47. Chaudhary K.W., Barrezueta N.X., Bauchmann M.B., Milici A.J., Beckius G., Stedman D.B., Hambor J.E., Blake W.L., McNeish J.D., Bahinski A., and Cezar G.G. Embryonic stem cells in predictive cardiotoxicity: laser capture microscopy enables assay development. Toxicol Sci 90 (2006) 149-158
48. Glatt H., Schneider H., and Liu Y. V79-hCYP2E1-hSULT1A1, a cell line for the sensitive detection of genotoxic effects induced by carbohydrate pyrolysis products and other food-borne chemicals. Mutat Res 580 (2005) 41-52
49. Corvi R. Genomics: an in vitro toxicology point of view. Altern Lab Anim 30 (2002) 129-131
50. Luhe A., Suter L., Ruepp S., Singer T., Weiser T., and Albertini S. Toxicogenomics in the pharmaceutical industry: hollow promises or real benefit?. Mutat Res 575 (2005) 102-115
51. Cimino M.C. Comparative overview of current international strategies and guidelines for genetic toxicology testing for regulatory purposes. Environ Mol Mutagen 47 (2006) 362-390
52. Sanguinetti M.C., and Tristani-Firouzi M. hERG potassium channels and cardiac arrhythmia. Nature 440 (2006) 463-469