Skip to main content
SpringerLink
Log in

Cytotoxicity and Genotoxicity Reporter Systems Based on the Use of Mammalian Cells

  • Chapter
  • First Online:
Whole Cell Sensing System II

Part of the book series: Advances in Biochemical Engineering / Biotechnology ((ABE,volume 118))

Abstract

With the dramatic increase in the number of new agents arising from the chemical, pharmaceutical, and agricultural industries, there is an urgent need to develop assays for rapid evaluation of potential risks to man and environment. The panel of conventional tests used for cytotoxicity and genotoxicity and the strategies to progress from small scale assays to high content screening in toxicology are discussed. The properties of components necessary as sensors and reporters for new reporter assays, and the application of genetic strategies to design assays are reviewed. The concept of cellular reporters is based on the use of promoters of chemical stress-regulated genes ligated to a suitable luminescent or fluorescent reporter gene. Current reporter assays designed from constructs transferred into suitable cell lines are presented.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Foth H, Hayes A (2008) Concept of REACH and impact on evaluation of chemicals. Hum Exp Toxicol 27:5–21

    Article  CAS  Google Scholar 

  2. Kirkland D, Aardema M, Henderson L, Müller L (2005) 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 predictivity. Mutat Res 584:1–256

    Article  CAS  Google Scholar 

  3. Kirkland D, Aardema M, Müller L, Makoto H (2006) Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens. II. Further analysis of mammalian cell results, relative predictivity and tumour profiles. Mutat Res 19:29–42

    Google Scholar 

  4. Trevan JW (1927) The error of determination of toxicity. Proc R Soc Ser B Biol Sci 101:483–514

    Article  CAS  Google Scholar 

  5. OECD (Organisation for Economic Cooperation and Development) (1987). Guideline for Testing of Chemicals – Acute Oral Toxicity. OECD Guideline 401

    Google Scholar 

  6. Cutler D (2001) Death of LD50. Trends Pharmacol Sci 22:62

    Google Scholar 

  7. OECD (Organisation for Economic Cooperation and Development) (2001). Updated guideline for testing of chemicals – acute oral toxicity-fixed dose method. OECD Guideline 420

    Google Scholar 

  8. OECD (Organisation for Economic Cooperation and Development) (2001). Updated guideline for the testing of chemicals – acute oral toxicity-acute toxic class method. OECD Guideline 423

    Google Scholar 

  9. OECD (Organisation for Economic Cooperation and Development) (1998). Guideline for the testing of chemicals – acute oral toxicity: up-and-down procedure. OECD Guideline 425

    Google Scholar 

  10. Goodman G, Wilson R (1999) Predicting the carcinogenicity of chemicals in humans from rodent bioassay data. Environ Health Perspect 94:195–218

    Article  Google Scholar 

  11. Monro A (1996) Are lifespan rodent carcinogenicity studies defensible for pharmaceutical agents? Exp Toxicol Pathol 48:155–166

    Article  CAS  Google Scholar 

  12. Rack L, Spira H (1989) Animal rights and modern toxicology. Toxicol Ind Health 5:133–143

    CAS  Google Scholar 

  13. Spielmann H (2002) A chair on alternatives? ALTEX 19:69–73

    Google Scholar 

  14. Balls M, Straughan DW (1996) The three Rs of Russell & Burch and the testing of biological products. Dev Biol Stand 86:11–18

    CAS  Google Scholar 

  15. Kreeftenberg JG (1999) Developments in the reduction refinement and replacement of animal tests in the quality control of immunobiologicals. Dev Biol Stand 101:17

    Google Scholar 

  16. van der Kamp MD (1996) Replacement, reduction or refinement of animal use in the quality control of veterinary vaccines: development, validation and implementation. Dev Biol Stand 86:73–76

    Google Scholar 

  17. Nath J, Krishna G (1998) Safety screening of drugs in cancer therapy. Acta Haematol 99:138–147

    Article  CAS  Google Scholar 

  18. Puck TT, Monro A (1955) A rapid method for viable cell titration and clone production with HeLa cells in tissue culture: the use of X-irradiated cells to supply conditioning factors. Proc Natl Acad Sci USA 103:432–437

    Article  Google Scholar 

  19. Puck TT, Monro A (1956) Action of X-rays on mammalian cells. J Exp Med 103:653–666

    Article  CAS  Google Scholar 

  20. Johnson TR, Massey RJ, Deinhardt F (1972) Lymphocyte and antibody cytotoxicity to tumor cells measured by a micro-51 chromium release assay. Immunol Commun 1:247–261

    CAS  Google Scholar 

  21. Zarling JM, McKeough M, Bach FH (1976) A sensitive micromethod for generating and assaying allogeneically induced cytotoxic human lymphocytes. Transplantation 21:468–476

    Article  CAS  Google Scholar 

  22. Mak S, Till JE (1963) Use of I-125-labeled 5-iodo-2′-deoxyuridine for the measurement of DNA synthesis in mammalian cells in vitro. Can J Biochem Physiol 41:2343–2351

    Article  CAS  Google Scholar 

  23. Kangas L, Grönroos M, Nieminen AL (1984) Bioluminescence of cellular ATP: a new method for evaluating cytotoxic agents in vitro. Med Biol 62:338–343

    CAS  Google Scholar 

  24. Kuzmits R, Aiginger P, Müller MM, Steurer G, Linkesch W (1986) Assessment of the sensitivity of leukaemic cells to cytotoxic drugs by bioluminescence measurement of ATP in cultured cells. Clin Sci 71:81–88

    CAS  Google Scholar 

  25. Lundin A, Hasenson M, Persson J, Pousette A (1986) Estimation of biomass in growing cell lines by adenosine triphosphate assay. Methods Enzymol 133:27–42

    Article  CAS  Google Scholar 

  26. Thore A, Anséhn S, Lundin A, Bergman S (1975) Detection of bacteriuria by luciferase assay of adenosine triphosphate. J Clin Microbiol 1:1–8

    CAS  Google Scholar 

  27. Untch M, Sevin BU, Perras JP, Angioli R, Untch A, Hightower RD, Koechli O, Averette HE (1994) Evaluation of paclitaxel (taxol), cisplatin, and the combination paclitaxel-cisplatin in ovarian cancer in vitro with the ATP cell viability assay. Gynecol Oncol 53:44–49

    Article  CAS  Google Scholar 

  28. Kurbacher CM, Cree IA (2005) Chemosensitivity testing using microplate adenosine triphosphate-based luminescence measurements. Methods Mol Med 110:101–120

    CAS  Google Scholar 

  29. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63

    Article  CAS  Google Scholar 

  30. Hayon T, Dvilansky A, Shpilberg O, Nathan I (2003) Appraisal of the MTT-based assay as a useful tool for predicting drug chemosensitivity in leukemia. Leuk Lymphoma 44:1957–1962

    Article  CAS  Google Scholar 

  31. Shimoyama Y, Kubota T, Watanabe M, Ishibiki K, Abe O (1989) Predictability of in vivo chemosensitivity by in vitro MTT assay with reference to the clonogenic assay. J Surg Oncol 41:12–18

    Article  CAS  Google Scholar 

  32. Borenfreund E, Babich H, Martin-Alguacil N (1990) Rapid chemosensitivity assay with human normal and tumor cells in vitro. In Vitro Cell Dev Biol 26:1030–1034

    Article  CAS  Google Scholar 

  33. Borenfreund E, Shopsis C (1985) Toxicity monitored with a correlated set of cell-culture assays. Xenobiotica 15:705–711

    Article  CAS  Google Scholar 

  34. Korzeniewski C, Callewaert DM (1983) An enzyme-release assay for natural cytotoxicity. J Immunol Methods 64:313–320

    Article  CAS  Google Scholar 

  35. Skreb Y, Habazin-Novak V (1975) Reversible inhibition of DNA, RNA and protein synthesis in human cells by lead chloride. Toxicology 5:167–174

    Article  CAS  Google Scholar 

  36. Rink H, Baumstark-Khan C, Partke HJ (1986) Radiation induced formation of giant cells (Saccharomyces uvarum): IV. Macromolecular synthesis and protein patterns. Radiat Environ Biophys 25:81–91

    Article  CAS  Google Scholar 

  37. Baumstark-Khan C, Hellweg CE, Scherer K, Horneck G (1999) Mammalian cells as biomonitors of UV-exposure. Anal Chim Acta 387:281–287

    Article  CAS  Google Scholar 

  38. Lockshin RA, Osborne B, Zakeri Z (2000) Cell death in the third millennium. Cell Death Differ 7:2–7

    Article  CAS  Google Scholar 

  39. Hetz C (2008) Apoptosis, necrosis and autophagy: from mechanisms to biomedical applications. Curr Mol Med 8:76–77

    Article  CAS  Google Scholar 

  40. Vermes I, Haanen C, Reutelingsperger C (2000) Flow cytometry of apoptotic cell death. J Immunol Methods 243:167–190

    Article  CAS  Google Scholar 

  41. Dearfield KL (1995) Information requirements and regulatory approaches for heritable genetic risk assessment and risk communication. Mutat Res 330:35–40

    Article  CAS  Google Scholar 

  42. Battershill JM, Fielder RJ (1998) Mouse-specific carcinogens: an assessment of hazard and significance for validation of short-term carcinogenicity bioassays in transgenic mice. Hum Exp Toxicol 17:193–205

    Article  CAS  Google Scholar 

  43. Bulman RA, Dragani TA, Bouffler SD, Cox R (2006) Locations of mouse DNA damage response and repair loci, and cancer risk modifiers. DNA Repair 5:274–277

    Article  CAS  Google Scholar 

  44. Naccarati A, Pardini B, Hemminki K, Vodicka P (2007) Sporadic colorectal cancer and individual susceptibility: a review of the association studies investigating the role of DNA repair genetic polymorphisms. Mutat Res 635:118–145

    Article  CAS  Google Scholar 

  45. Pastwa E, Somiari RI, Malinowski M, Somiari SB, Winters TA (2009) In vitro non-homologous DNA end joining assays ─ the 20th anniversary. Int J Biochem Cell Biol 41:1254–1260

    Google Scholar 

  46. Hoeijmakers JHJ (2001) Genome maintenance mechanisms for preventing cancer. Nature 411:366–374

    Article  CAS  Google Scholar 

  47. Baumstark-Khan C (1993) X-ray-induced DNA double-strand breaks as lethal lesions in diploid human fibroblasts compared to chinese hamster ovary cells. Int J Radiat Biol 63:305–311

    Article  CAS  Google Scholar 

  48. Baumstark-Khan C (1992) Effect of aphidicolin on DNA synthesis, PLD recovery and DNA repair of a human diploid cell line. Int J Radiat Biol 61:191–197

    Article  CAS  Google Scholar 

  49. Blöcher D, Pohlit W (1982) DNA double strand breaks in Ehrlich ascites tumour cells at low doses of X-rays. II. Can cell death be attributed to double strand breaks? Int J Radiat Biol 42:329–338

    Article  Google Scholar 

  50. Shuker DE, Farmer PB (1992) Relevance of urinary DNA adducts as markers of carcinogen exposure. Chem Res Toxicol 5:450–460

    Article  CAS  Google Scholar 

  51. Poirier MC, Yuspa SH, Weinstein IB, Blobstein S (1977) Detection of carcinogen-DNA adducts by radiommunoassay. Nature 270:186–188

    Article  CAS  Google Scholar 

  52. Poirier MC, Santella RM, Weinstein IB, Grunberger D, Yuspa SH (1980) Quantitation of benzo[a]pyrene-deoxyguanosine adducts by radioimmunoassay. Cancer Res 40:412–416

    CAS  Google Scholar 

  53. Baan RA, Zaalberg OB, Fichtinger-Schepman AM, Muysken-Schoen MA, Lansbergen MJ, Lohman PH (1985) Use of monoclonal and polyclonal antibodies against DNA adducts for the detection of DNA lesions in isolated DNA and in single cells. Environ Health Perspect 62:88

    Article  Google Scholar 

  54. Santella RM (1988) Monitoring human exposure to carcinogens by DNA adduct measurement. Cell Biol Toxicol 4:511–516

    Article  CAS  Google Scholar 

  55. Santella RM (1999) Immunological methods for detection of carcinogen-DNA damage in humans. Cancer Epidemiol Biomarkers Prev 8:733–739

    CAS  Google Scholar 

  56. Reddy MV (2000) Methods for testing compounds for DNA adduct formation. Regul Toxicol Pharmacol 32:256–263

    Article  CAS  Google Scholar 

  57. Reddy MV, Randerath K (1987) 32P-postlabeling assay for carcinogen-DNA adducts: nuclease P1-mediated enhancement of its sensitivity and applications. Environ Health Perspect 76:41–47

    CAS  Google Scholar 

  58. Kumar R, Singh SK, Kole PL, Elmarakby S, Sikka HC (1995) Stereoselective metabolism of dibenz[a, h]acridine to bay-region diol epoxides by rat liver microsomes. Carcinogenesis 16:525–5130

    Article  CAS  Google Scholar 

  59. Kurisu S, Miya T, Terato H, Masaoka A, Ohyama Y, Kubo K, Ide H (2001) Quantitation of DNA damage by an aldehyde reactive probe (ARP). Nucleic Acids Symp Ser 1:45–46

    Article  Google Scholar 

  60. Nakamura J, Walker VE, Upton PB, Chiang SY, Kow YW, Swenberg JA (1998) Highly sensitive apurinic/apyrimidinic site assay can detect spontaneous and chemically induced depurination under physiological conditions. Cancer Res 15:222–225

    Google Scholar 

  61. Thompson LH, West MG (2000) XRCC1 keeps DNA from getting stranded. Mutat Res 459:1–18

    Article  CAS  Google Scholar 

  62. Morgan WF, Corcoran J, Hartmann A, Kaplan MI, Limoli CL, Ponnaiya B (1998) DNA double-strand breaks, chromosomal rearrangements, and genomic instability. Mutat Res 404:125–128

    Article  CAS  Google Scholar 

  63. Iliakis G, Blöcher D, Metzger L, Pantelias G (1991) Comparison of DNA double-strand break rejoining as measured by pulsed field gel electrophoresis, neutral sucrose gradient centrifugation and non-unwinding filter elution in irradiated plateau-phase CHO cells. Int J Radiat Biol 59:927–939

    Article  CAS  Google Scholar 

  64. Daniel FB, Haas DL, Pyle SM (1985) Quantitation of chemically induced DNA strand breaks in human cells via an alkaline unwinding assay. Anal Biochem 144:390–402

    Article  CAS  Google Scholar 

  65. Dusinská M, Slamenová D (1992) Application of alkaline unwinding assay for detection of mutagen-induced DNA strand breaks. Cell Biol Toxicol 8:207–216

    Article  Google Scholar 

  66. Ahnström G, Erixon K (1973) Radiation-induced strand breakage in DNA from mammalian cells: strand separation in alkaline solution. Int J Radiat Biol 23:285–289

    Article  Google Scholar 

  67. Baumstark-Khan C, Griesenbach U, Rink H (1992) Comparison of DNA strand break induction in CHO cells measured by alkaline elution and by fluorometric analysis of DNA unwinding (FADU). Free Radic Res Commun 16:381–389

    Article  CAS  Google Scholar 

  68. Baumstark-Khan C, Hentschel U, Nikandrova Y, Krug J, Horneck G (2000) Fluorometric analysis of DNA unwinding (FADU) as a method for detecting repair-induced DNA strand breaks in UV-irradiated mammalian cells. Photochem Photobiol 72:477–484

    Article  CAS  Google Scholar 

  69. Baumstark-Khan C, Nikandrova Y, Krug J, Hentschel U, Horneck G (1999) Adaptation of the fluorometric analysis of DNA unwinding (FADU) for the detection of repair-induced DNA strand breaks after UV-irradiation of mammalian cells. Trends Photochem Photobiol 6:141–152

    CAS  Google Scholar 

  70. Birnboim HC, Jevcak JJ (1981) Fluorometric method for rapid detection of DNA strand breaks in human white blood cells produced by low doses of radiation. Cancer Res 41:1889–1892

    CAS  Google Scholar 

  71. Elmendorff-Dreikorn K, Chauvin C, Slor H, Kutzner J, Batel R, Müller WE, Schröder HC (1999) Assessment of DNA damage and repair in human peripheral blood mononuclear cells using a novel DNA unwinding technique. Cell Mol Biol 45:211–218

    CAS  Google Scholar 

  72. Kanter PM, Schwartz HS (1982) A fluorescence enhancement assay for cellular DNA damage. Mol Pharmacol 22:145–151

    CAS  Google Scholar 

  73. Korba BE, Hays JB, Boehmer S (1981) Sedimentation velocity of DNA in isokinetic sucrose gradients: calibration against molecular weight using fragments of defined length. Nucleic Acids Res 9:4403–4412

    Article  CAS  Google Scholar 

  74. McGrath RA, Williams RW (1966) Reconstruction in vivo of irradiated Escherichia coli deoxyribonucleic acid; the rejoining of broken pieces. Nature 212:534–535

    Article  CAS  Google Scholar 

  75. Crump PW, Fielden EM, Jenner TJ, O’Neill P (1990) A comparison of the techniques of alkaline filter elution and alkaline sucrose sedimentation used to assess DNA damage induced by 2-nitroimidazoles. Biochem Pharmacol 40:621–627

    Article  CAS  Google Scholar 

  76. Kohn KW, Grimek-Ewig RA (1973) Alkaline elution analysis, a new approach to the study of DNA single-strand interruptions in cells. Cancer Res 33:1849–1853

    CAS  Google Scholar 

  77. Sutherland JC, Monteleone DC, Mugavero JH, Trunk J (1987) Unidirectional pulsed-field electrophoresis of single- and double-stranded DNA in agarose gels: analytical expressions relating mobility and molecular length and their application in the measurement of strand breaks. Anal Biochem 162:511–520

    Article  CAS  Google Scholar 

  78. Lu J, Kaeck MR, Jiang C, Garcia G, Thompson HJ (1996) A filter elution assay for the simultaneous detection of DNA double and single strand breaks. Anal Biochem 235:227–233

    Article  CAS  Google Scholar 

  79. Olive PL (2009) Impact of the comet assay in radiobiology. Mutat Res 681:13–23

    Article  CAS  Google Scholar 

  80. Olive PL (2002) The comet assay. An overview of techniques. Methods Mol Biol 203:179–194

    CAS  Google Scholar 

  81. Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191

    Article  CAS  Google Scholar 

  82. Olive PL, Banáth JP (2009) Radiation-induced DNA double-strand breaks produced in histone-depleted tumor cell nuclei measured using the neutral comet assay. Radiat Res 142:144–152

    Article  Google Scholar 

  83. Gedik CM, Ewen SW, Collins AR (1992) Single-cell gel electrophoresis applied to the analysis of UV-C damage and its repair in human cells. Int J Radiat Biol 62:313–320

    Article  CAS  Google Scholar 

  84. De Boeck M, Touil N, De Visscher G, Vande PA, Kirsch-Volders M (2000) Validation and implementation of an internal standard in comet assay analysis. Mutat Res 469:181–197

    Article  Google Scholar 

  85. Collins AR, Dobson VL, Dusinská M, Kennedy G, Stetina R (1997) The comet assay: what can it really tell us? Mutat Res 375:183–193

    Article  CAS  Google Scholar 

  86. Collins AR, Dusinská M, Horská A (2001) Detection of alkylation damage in human lymphocyte DNA with the comet assay. Acta Biochim Pol 48:611–614

    CAS  Google Scholar 

  87. Piersen CE, McCullough AK, Lloyd RS (2000) AP lyases and dRPases: commonality of mechanism. Mutat Res 459:43–53

    Article  CAS  Google Scholar 

  88. Girard PM, D’Ham C, Cadet J, Boiteux S (1998) Opposite base-dependent excision of 7, 8-dihydro-8-oxoadenine by the Ogg1 protein of Saccharomyces cerevisiae. Carcinogenesis 19:1299–1305

    Article  CAS  Google Scholar 

  89. Mohsin Ali M, Kurisu S, Yoshioka Y, Terato H, Ohyama Y, Kubo K, Ide H (2004) Detection of endonuclease III- and 8-oxoguanine glycosylase-sensitive base modifications in gamma-irradiated DNA and cells by the aldehyde reactive probe (ARP) assay. J Radiat Res 45:229–237

    Article  CAS  Google Scholar 

  90. Bonassi S, Ugolini D, Kirsch-Volders M, Strömberg U, Vermeulen R, Tucker JD (2005) Human population studies with cytogeneticbiomarkers: review of the literature and future prospectives. Environ Mol Mutagen 45:258–270

    Article  CAS  Google Scholar 

  91. Norppa H, Bonassi S, Hansteen IL, Hagmar L, Strömberg U, Rössner P, Boffetta P, Lindholm C, Gundy S, Lazutka J, Cebulska-Wasilewska A, Fabiánová E, Srám RJ, Knudsen LE, Barale R, Fucic A (2006) Chromosomal aberrations and SCEs as biomarkers of cancer risk. Mutat Res 600:37–45

    Article  CAS  Google Scholar 

  92. van Delft JH, Baan RA, Roza L (1998) Biological effect markers for exposure to carcinogenic compound and their relevance for risk assessment. Crit Rev Toxicol 28:477–510

    Article  Google Scholar 

  93. Clements J (1995) Gene mutation assays in mammalian cells. Methods Mol Biol 43:277–286

    CAS  Google Scholar 

  94. O’Neill JP, Brimer PA, Machanoff R, Hirsch GP, Hsie AW (2009) A quantitative assay of mutation induction at the hypoxanthine-guanine phosphoribosyl transferase locus in Chinese hamster ovary cells (CHO/HGPRT system): development and definition of the system. Mutat Res 45:91–101

    Google Scholar 

  95. Kirkland DJ, Clements J (1998) Recommendations for spacing of test chemical concentrations in the mouse lymphomatk mutation assay (MLA). Mutat Res 415:159–163

    Article  CAS  Google Scholar 

  96. Mitchell AD, Auletta AE, Clive D, Kirby PE, Moore MM, Myhr BC (1997) The L5178Y/tk+/− mouse lymphoma specific gene and chromosomal mutation assay aphase III report of the U.S. Environmental Protection Agency Gene-Tox Program. Mutat Res 394:177–303

    Article  CAS  Google Scholar 

  97. Wang J, Heflich RH, Moore MM (2007) A method to distinguish between the de novo induction of thymidine kinase mutants and the selection of pre-existing thymidine kinase mutants in the mouse lymphoma assay. Mutat Res 626:185–190

    Article  CAS  Google Scholar 

  98. Corsaro CM, Migeon BR (1977) Contact-mediated communication of ouabain resistance in mammalian cells in culture. Nature 268:737–739

    Article  CAS  Google Scholar 

  99. Dayan J, Deguingand S, Truzman C (1985) Study of the mutagenic activity of 6 hepatotoxic pharmaceutical drugs in the Salmonella typhimurium microsome test, and the HGPRT and Na+/K+ ATPase system in cultured mammalian cells. Mutat Res 157:1–12

    Article  CAS  Google Scholar 

  100. Moore MM, Harrington-Brock K, Doerr CL, Dearfield KL (1989) Differential mutant quantitation at the mouse lymphoma tk and CHO hgprt loci. Mutagenesis 4:394–403

    Article  CAS  Google Scholar 

  101. Li AP, Aaron CS, Auletta AE, Dearfield KL, Riddle JC, Slesinski RS, Jr StankowskiLF (1991) An evaluation of the roles of mammalian cell mutationassays in the testing of chemical genotoxicity. Regul Toxicol Pharmacol 14:24–40

    Article  CAS  Google Scholar 

  102. Puck TT, Waldren CA (1987) Mutation in mammalian cells: theory and implications. Somatic Cell Mol Genet 13:405–409

    Article  CAS  Google Scholar 

  103. Waldren C, Jones C, Puck TT (1979) Measurement of mutagenesis in mammalian cells. Proc Natl Acad Sci USA 76:1358–1362

    Article  CAS  Google Scholar 

  104. Ross CD, Lim CU, Fox MH (2005) Assay to measure CD59 mutations in CHO A(L) cells using flow cytometry. Cytometry Part A 66:85–90

    Article  CAS  Google Scholar 

  105. Zhou H, Xu A, Gillispie JA, Waldren CA, Hei TK (2006) Quantification of CD59-mutants in human-hamster hybrid (AL) cells by flow cytometry. Mutat Res 594:113–119

    Article  CAS  Google Scholar 

  106. Baumstark-Khan C (2009) A calculation method of PLD recovery based on saturation kinetics. In: Riklis E (ed) Frontiers in radiation biology. VCH & Balaban, Weinheim, pp 513–520

    Google Scholar 

  107. Dikomey E, Franzke J (1986) DNA repair kinetics after exposure to X-irradiation and to internal beta-rays in CHO cells. Radiat Environ Biophys 25:189–194

    Article  CAS  Google Scholar 

  108. Dikomey E, Franzke J (1986) Three classes of DNA strand breaks induced by X-irradiation and internal beta-rays. Int J Radiat Biol 50:893–908

    Article  CAS  Google Scholar 

  109. Weibezahn KF, Coquerelle T (1981) Radiation induced DNA double strand breaks are rejoined by ligation and recombination processes. Nucleic Acids Res 9:3139–3150

    Article  CAS  Google Scholar 

  110. Madle S, Dean SW, Andrae U, Brambilla G, Burlinson B, Doolittle DJ, Furihata C, Hertner T, McQueen CA, Mori H (1994) Recommendations for the performance of UDS tests in vitro and in vivo. Mutat Res 312:263–285

    Article  CAS  Google Scholar 

  111. Mitchell AD, Casciano DA, Meltz ML, San RH, Williams GM, von Halle ES (1983) Unscheduled DNA synthesis tests. A report of the U.S. Environmental protection agency gene-tox program. Mutat Res 123:363–410

    Article  CAS  Google Scholar 

  112. Efeyan A, Serrano M (2007) p53: guardian of the genome and policeman of the oncogenes. Cell Cycle 6:1006–1010

    Article  CAS  Google Scholar 

  113. Gomez-Lazaro M, Fernandez-Gomez FJ, Jordán J (2004) p53: twenty five years understanding the mechanism of genome protection. J Physiol Biochem 60:287–307

    Article  CAS  Google Scholar 

  114. Janus F, Albrechtsen N, Dornreiter I, Wiesmüller L, Grosse F, Deppert W (1999) The dual role model for p53 in maintaining genomic integrity. Cell Mol Life Sci 55:12–27

    Article  CAS  Google Scholar 

  115. Wu X, Ranganathan V, Weisman DS, Ciccone DN, O’Neill TB, Crick KE, Pierce KA, Lane WS, Rathbun G, Livingston DM, Weaver DT (2000) ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response. Nature 405:477–482

    Article  CAS  Google Scholar 

  116. Lee H, Kwak HJ, Cho IT, Park SH, Lee CH (2009) S1219 residue of 53BP1 is phosphorylated by ATM kinase upon DNA damage and required for proper execution of DNA damage response. Biochem Biophys Res Commun 378:32–36

    Article  CAS  Google Scholar 

  117. Xu B, O’Donnell AH, Kim ST, Kastan MB (2002) Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation. Cancer Res 62:4588–4591

    CAS  Google Scholar 

  118. O’Reilly MA (2005) Redox activation of p21Cip1/WAF1/Sdi1: a multifunctional regulator of cell survival and death. Antioxid Redox Signal 7:108–118

    Article  Google Scholar 

  119. Mazumder S, Plesca D, Almasan A (2007) A jekyll and hyde role of cyclin E in the genotoxic stress response: switching from cell cycle control to apoptosis regulation. Cell Cycle 6:1437–1442

    Article  CAS  Google Scholar 

  120. Mukherjee B, Kessinger C, Kobayashi J, Chen BP, Chatterjee A, Burma S (2006) DNA-PK phosphorylates histone H2AX during apoptotic DNA fragmentation in mammalian cells. DNA Repair 5:575–590

    Article  CAS  Google Scholar 

  121. Liebermann DA, Hoffman B (2008) Gadd45 in stress signaling. J Mol Signal 3:15

    Article  CAS  Google Scholar 

  122. Solier S, Sordet O, Kohn KW, Pommier Y (2009) Death receptor-induced activation of the Chk2- and histone H2AX-associated DNA damage response pathways. Mol Cell Biol 29:68–82

    Article  CAS  Google Scholar 

  123. Scholzen T, Gerdes J (2000) The Ki-67 protein: from the known and the unknown. J Cell Physiol 182:311–322

    Article  CAS  Google Scholar 

  124. Wu X, Lieber MR (1996) Protein-protein and protein-DNA interaction regions within the DNA end-binding protein Ku70-Ku86. Mol Cell Biol 16:5186–5193

    CAS  Google Scholar 

  125. Agrawal A, Yang J, Murphy RF, Agrawal DK (2006) Regulation of the p14ARF-Mdm2–p53 pathway: an overview in breast cancer. Environ Mol Pathol 81:115–122

    Article  CAS  Google Scholar 

  126. Williams RS, Williams JS, Tainer JA (2007) Mre11-Rad50-Nbs1 is a keystone complex connecting DNA repair machinery, double-strand break signaling, and the chromatin template. Biochem Cell Biol 85:509–520

    Article  CAS  Google Scholar 

  127. Marcelain K, De La Torre C, González P, Pincheira J (2009) Roles of nibrin and AtM/ATR kinases on the G2 checkpoint under endogenous or radio-induced DNA damage. Biol Res 38:179–185

    Google Scholar 

  128. Besson A, Yong VW (2001) Mitogenic signaling and the relationship to cell cycle regulation in astrocytomas. J Neurooncol 51:245–264

    Article  CAS  Google Scholar 

  129. Essers J, Theil AF, Baldeyron C, van Cappellen WA, Houtsmuller AB, Kanaar R, Vermeulen W (2005) Nuclear dynamics of PCNA in DNA replication and repair. Mol Cell Biol 25:9350–9359

    Article  CAS  Google Scholar 

  130. Digweed M, Rothe S, Demuth I, Scholz R, Schindler D, Stumm M, Grompe M, Jordan A, Sperling K (2002) Attenuation of the formation of DNA-repair foci containing RAD51 in Fanconi anaemia. Carcinogenesis 23:1121–1126

    Article  CAS  Google Scholar 

  131. Meek DW (1994) Post-translational modification of p53. Semin Cancer Biol 5:203–210

    CAS  Google Scholar 

  132. Rocha S, Garrett MD, Campbell KJ, Schumm K, Perkins ND (2005) Regulation of NF-kappaB and p53 through activation of ATR and Chk1 by the ARF tumour suppressor. EMBO J 24:1157–1169

    Article  CAS  Google Scholar 

  133. Pilch DR, Sedelnikova OA, Redon C, Celeste A, Nussenzweig A, Bonner WM (2003) Characteristics of gamma-H2AX foci at DNA double-strand breaks sites. Biochem Cell Biol 81:123–129

    Article  CAS  Google Scholar 

  134. Iijima K, Ohara M, Seki R, Tauchi H (2008) Dancing on damaged chromatin: functions of ATM and the RAD50/MRE11/NBS1 complex in cellular responses to DNA damage. J Radiat Res 49:451–464

    Article  CAS  Google Scholar 

  135. Kang J, Ferguson D, Song H, Bassing C, Eckersdorff M, Alt FW, Xu Y (2009) Functional interaction of H2AX, NBS1, and p53 in ATM-dependent DNA damage responses and tumor suppression. Mol Cell Biol 25:661–670

    Article  CAS  Google Scholar 

  136. Ward IM, Minn K, Jorda KG, Chen J (2003) Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphorylated histone H2AX. J Biol Chem 278:19579–19582

    Article  CAS  Google Scholar 

  137. Rashi-Elkeles S, Elkon R, Weizman N, Linhart C, Amariglio N, Sternberg G, Rechavi G, Barzilai A, Shamir R, Shiloh Y (2006) Parallel induction of ATM-dependent pro- and antiapoptotic signals in response to ionizing radiation in murine lymphoid tissue. Oncogene 25:1584–1592

    Article  CAS  Google Scholar 

  138. Feng Z, Hu W, Rajagopal G, Levine AJ (2008) The tumor suppressor p53: cancer and aging. Cell Cycle 7:842–847

    Article  CAS  Google Scholar 

  139. Gottlieb TM, Oren M (1996) p53 in growth control and neoplasia. Biochim Biophys Acta 1287:77–102

    Google Scholar 

  140. Dulic V, Kaufmann WK, Wilson SJ, Tlsty TD, Lees E, Harper JW, Elledge SJ, Reed SI (2009) p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell 76:1013–1023

    Article  Google Scholar 

  141. Karin M, Lin A (2002) NF-kappaB at the crossroads of life and death. Nat Immunol 3:221–227

    Article  CAS  Google Scholar 

  142. Papa S, Zazzeroni F, Pham CG, Bubici C, Franzoso G (2004) Linking JNK signaling to NF-kappaB: a key to survival. J Cell Sci 117:5197–5208

    Article  CAS  Google Scholar 

  143. Habraken Y, Piette J (2006) NF-kappaB activation by double-strand breaks. Biochem Pharmacol 72:1132–1141

    Article  CAS  Google Scholar 

  144. Oberst A, Bender C, Green DR (2008) Living with death: the evolution of the mitochondrial pathway of apoptosis in animals. Cell Death Different 15:1139–1146

    Article  CAS  Google Scholar 

  145. Abu-Qare AW, Abou-Donia MB (2001) Biomarkers of apoptosis: release of cytochrome c, activation of caspase-3, induction of 8-hydroxy-2′-deoxyguanosine, increased 3-nitrotyrosine, and alteration of p53 gene. J Toxicol Environ Health Part B Crit Rev 4:313–332

    Article  CAS  Google Scholar 

  146. Bradbury DA, Simmons TD, Slater KJ, Crouch SP (2000) Measurement of the ADP:ATP ratio in human leukaemic cell lines can be used as an indicator of cell viability, necrosis and apoptosis. J Immunol Methods 240:79–92

    Article  CAS  Google Scholar 

  147. Sundberg SA (2000) High-throughput and ultra-high-throughput screening: solution- and cell-based approaches. Curr Opin Biotechnol 11:47–53

    Article  CAS  Google Scholar 

  148. Fischbach M, Bromley P (2001) Recombinant cell lines for stress reporter assays. Cell Biol Toxicol 17:335–351

    Article  CAS  Google Scholar 

  149. King AV, Jones PA (2003) In-house assessment of a modified in vitro cytotoxicity assay for higher throughput estimation of acute toxicity. Toxicol In Vitro 17:717–722

    Article  CAS  Google Scholar 

  150. Alley MC, Scudiero DA, Monks A, Hursey ML, Czerwinski MJ, Fine DL, Abbott BJ, Mayo JG, Shoemaker RH, Boyd MR (1988) Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res 48:589–601

    CAS  Google Scholar 

  151. Riss TL, Moravec RA (2004) Use of multiple assay endpoints to investigate the effects of incubation time, dose of toxin, and plating density in cell-based cytotoxicity assays. Assay Drug Dev Technol 2:51–62

    Article  CAS  Google Scholar 

  152. Jost LM, Kirkwood JM, Whiteside TL (1992) Improved short- and long-term XTT-based colorimetric cellular cytotoxicity assay for melanoma and other tumor cells. J Immunol Methods 147:153–165

    Article  CAS  Google Scholar 

  153. Fan F, Wood KV (2007) Bioluminescent assays for high-throughput screening. Assay Drug Dev Technol 5:127–136

    Article  CAS  Google Scholar 

  154. Wesierska-Gadek J, Gueorguieva M, Ranftler C, Zerza-Schnitzhofer G (2005) A new multiplex assay allowing simultaneous detection of the inhibition of cell proliferation and induction of cell death. J Cell Biochem 96:1–7

    Article  CAS  Google Scholar 

  155. O’Brien MA, Moravec RA, Riss TL, Bulleit RF (2008) Homogeneous, bioluminescent proteasome assays. Methods Mol Biol 414:163–181

    Google Scholar 

  156. Baumstark-Khan C, Horneck G (2007) Results from the “Technical workshop on genotoxicity biosensing” on the microscale fluorometric assay of DNA-unwinding. Anal Chim Acta 593:75–81

    Article  CAS  Google Scholar 

  157. Ullmann K, Müller C, Steinberg P (2008) Two essential modifications strongly improve the performance of the Fast Micromethod to identify DNA single- and double-strand breaks. Arch Toxicol 82:861–867

    Article  CAS  Google Scholar 

  158. Frieauff W, Hartmann A, Suter W (2001) Automatic analysis of slides processed in the comet assay. Mutagenesis 15:133–137

    Article  Google Scholar 

  159. Kiskinis E, Suter W, Hartmann A (2002) High throughput comet assay using 96-well plates. Mutagenesis 17:37–43

    Article  CAS  Google Scholar 

  160. Ashcroft R, Lopez P (2000) Commercial high speed machines opennew opportunities in high throughput flow cytometry (HTFC). J Immunol Methods 243:13–24

    Article  CAS  Google Scholar 

  161. Forand A, Dutrillaux B, Bernardino-Sgherri J (2004) Gamma-H2AX expression pattern in non-irradiated neonatal mouse germ cells and after low-dose gamma-radiation: relationships between chromatid breaks and DNA double-strand breaks. Biol Reprod 71:643–649

    Article  CAS  Google Scholar 

  162. Abraham VC, Taylor DL, Haskins JR (2004) High content screening applied to large-scale cell biology. Trends Biotechnol 22:15–22

    Article  CAS  Google Scholar 

  163. Cervinka M, Cervinkova Z, Rudolf E (2008) The role of time-lapse fluorescent microscopy in the characterization of toxic effects in cell populations cultivated in vitro. Toxicol In Vitro 22:1382–1386

    Article  CAS  Google Scholar 

  164. Evans JG, Matsudaira P (2007) Linking microscopy and high content screening in large-scale biomedical research. Methods Mol Biol 356:33–38

    Google Scholar 

  165. Rausch O (2006) High content cellular screening. Curr Opin Chem Biol 10:316–329

    Article  CAS  Google Scholar 

  166. Diaz D, Scott A, Carmichael P, Shi W, Costales C (2007) Evaluation of an automated in vitro micronucleus assay in CHO-K1 cells. Mutat Res 630:1–13

    Article  CAS  Google Scholar 

  167. He YD (2006) Genomic approach to biomarker identification and its recent applications. Cancer Biomarkers 2:103–133

    CAS  Google Scholar 

  168. Leighton JK (2005) Application of emerging technologies in toxicology and safety assessment: regulatory perspectives. Int J Toxicol 24:153–155

    Article  Google Scholar 

  169. Aardema MJ, MacGregor JT (2002) Toxicology and genetic toxicology in the new era of “toxicogenomics”: impact of “-omics” technologies. Mutat Res 499:13–25

    Article  CAS  Google Scholar 

  170. Waters MD, Fostel JM (2004) Toxicogenomics and systems toxicology: aims and prospects. Nat Rev Genet 5:936–948

    Article  CAS  Google Scholar 

  171. Xu ZL, Mizuguchi H, Ishii-Watabe A, Uchida E, Mayumi T, Hayakawa T (2001) Optimization of transcriptional regulatory elements for constructing plasmid vectors. Gene 272:149–156

    Article  CAS  Google Scholar 

  172. López-Maury L, Marguerat S, Bähler J (2008) Tuning gene expression to changing environments: from rapid responses to evolutionary adaptation. Nat Rev Genet 9:583–593

    Article  CAS  Google Scholar 

  173. Edelman GM, Meech R, Owens GC, Jones FS (2000) Synthetic promoter elements obtained by nucleotide sequence variation and selection for activity. Proc Nat Acad Sci USA 97:3038–3043

    Article  CAS  Google Scholar 

  174. Alcaraz-Pérez F, Mulero V, Cayuela ML (2008) Application of the dual-luciferase reporter assay to the analysis of promoter activity in Zebrafish embryos. BMC Biotechnol 8:81

    Article  CAS  Google Scholar 

  175. Arnone MI, Dmochowski IJ, Gache C (2004) Using reporter genes to study cis-regulatory elements. Methods Cell Biol 74:652

    Google Scholar 

  176. Schlaeger EJ, Kitas EA, Dorn A (2003) SEAP expression in transiently transfected mammalian cells grown in serum-free suspension culture. Cytotechnology 42:47–55

    Article  CAS  Google Scholar 

  177. Michelini E, Cevenini L, Mezzanotte L, Ablamsky D, Southworth T, Branchini BR, Roda A (2008) Combining intracellular and secreted bioluminescent reporter proteins for multicolor cell-based assays. Photochem Photobiol Sci 7:212–217

    Article  CAS  Google Scholar 

  178. Tannous BA, Kim DE, Fernandez JL, Weissleder R, Breakefield XO (2005) Codon-optimized Gaussia luciferase cDNA for mammalian gene expression in culture and in vivo. Mol Ther 11:435–443

    Article  CAS  Google Scholar 

  179. Baumstark-Khan C, Hellweg CE, Horneck G (2002) On the suitability of red and enhanced green fluorescent protein (DsRed/EGFP) as reporter combination. In: Hoffmann K-H (ed), Springer, Berlin, pp 1–13

    Google Scholar 

  180. Hellweg CE, Baumstark-Khan C, Rettberg P, Horneck G (2001) The suitability of enhanced green fluorescent protein (EGFP) as reporter component for bioassays. Anal Chim Acta 426:175–184

    Article  CAS  Google Scholar 

  181. Shaner NC, Steinbach PA, Tsien RY (2005) A guide to choosing fluorescent proteins. Nat Methods 2:905–909

    Article  CAS  Google Scholar 

  182. Jeng MH, Shupnik MA, Bender TP, Westin EH, Bandyopadhyay D, Kumar R, Masamura S, Santen RJ (1998) Estrogen receptor expression and function in long-term estrogen-deprived human breast cancer cells. Endocrinology 139:4164–4174

    Article  CAS  Google Scholar 

  183. Donato MT, Lahoz A, Castell JV, Gómez-Lechón MJ (2008) Cell lines: a tool for in vitro drug metabolism studies. Curr Drug Metab 9:1–11

    Article  CAS  Google Scholar 

  184. Scheuenpflug J, Krebsfänger N, Doehmer J (2005) Heterologous co-expression of human cytochrome P450 1A2 and polymorphic forms of N-acetyltransferase 2 for studies on aromatic amines in V79 Chinese hamster cells. Altern Lab Anim 33:561–577

    CAS  Google Scholar 

  185. Zhuge J, Luo Y, Yu YN (2003) Heterologous expression of human cytochrome P450 2E1 in HepG2 cell line. World J Gastroenterol 9:2732–2736

    CAS  Google Scholar 

  186. Guillouzo A, Corlu A, Aninat C, Glaise D, Morel F, Guguen-Guillouzo C (2007) The human hepatoma HepaRG cells: a highly differentiated model for studies of liver metabolism and toxicity of xenobiotics. Chem-Biol Interact 168:66–73

    Article  CAS  Google Scholar 

  187. Chen JJ (2007) Key aspects of analyzing microarray gene-expression data. Pharmacogenomics 8:473–482

    Article  CAS  Google Scholar 

  188. Lettieri T (2006) Recent applications of DNA microarray technology to toxicology and ecotoxicology. Environ Health Perspect 114:4–9

    CAS  Google Scholar 

  189. Coombe DR, Nakhoul AM, Stevenson SM, Peroni SE, Sanderson CJ (1998) Expressed luciferase viability assay (ELVA) for the measurement of cell growth and viability. J Immunol Methods 215:145–150

    Article  CAS  Google Scholar 

  190. Elliott G, McGrath J, Crockett-Torabi E (2000) Green fluorescent protein: a novel viability assay for cryobiological applications. Cryobiology 40:360–369

    Article  CAS  Google Scholar 

  191. Baumstark-Khan C, Hellweg CE, Palm M, Horneck G (2001) Enhanced green fluorescent protein (EGFP) for space radiation research using mammalian cells in the International Space Station. Phys Med 17:210–214

    Google Scholar 

  192. Hellweg CE, Baumstark-Khan C, Horneck G (2001) Enhanced green fluorescent protein as reporter protein for biomonitoring of cytotoxic effects in mammalian cells. Anal Chim Acta 427:191–199

    Article  CAS  Google Scholar 

  193. Hellweg CE, Arenz A, Baumstark-Khan C (2007) Assessment of space environmental factors by cytotoxicity bioassays. Acta Astronaut 60:525–533

    Article  CAS  Google Scholar 

  194. Quiñones A, Rainov NG (2001) Identification of genotoxic stress in human cells by fluorescent monitoring of p53 expression. Mutat Res 494:73–85

    Article  Google Scholar 

  195. Gorbunov NV, Morris JE, Greenberger JS, Thrall BD (2002) Establishment of a novel clonal murine bone marrow stromal cell line for assessment of p53 responses to genotoxic stress. Toxicology 179:257–266

    Article  CAS  Google Scholar 

  196. Ohno K, Ishihata K, Tanaka-Azuma Y, Yamada T (2008) A genotoxicity test system based on p53R2 gene expression in human cells: assessment of its reactivity to various classes of genotoxic chemicals. Mutat Res 656:27–35

    Article  CAS  Google Scholar 

  197. Ohno K, Tanaka-Azuma Y, Yoneda Y, Yamada T (2005) Genotoxicity test system based on p53R2 gene expression in human cells: examination with 80 chemicals. Mutat Res 588:47–57

    Article  CAS  Google Scholar 

  198. Arenz A (2007) Design and validation of a bioassay for detection of induced gene activity to be used at the International Space Station, Faculty of Mathematics and Natural Sciences, University of Cologne, Germany

    Google Scholar 

  199. Hellweg CE, Baumstark-Khan C, Horneck G (2003) Generation of stably transfected mammalian cell lines as fluorescent screening assay for NF-kappaB activation-dependent gene expression. J Biomol Screening 8:511–521

    Article  CAS  Google Scholar 

  200. Hellweg CE, Arenz A, Bogner S, Schmitz C, Baumstark-Khan C (2006) Activation of nuclear factor kappa B by different agents: influence of culture conditions in a cell-based assay. Ann NY Acad Sci 1091:191–204

    Article  CAS  Google Scholar 

  201. Baumstark-Khan C, Hellweg CE, Arenz A, Meier MM (2005) Cellular monitoring of the nuclear factor kappaB pathway for assessment of space environmental radiation. Radiat Res 1664:527–530

    Article  Google Scholar 

  202. Hellweg CE, Baumstark-Khan C (2007) Detection of UV-induced activation of NF-kappaB in a recombinant human cell line by means of enhanced green fluorescent protein (EGFP). Radiat Environ Biophys 46:269–279

    Article  CAS  Google Scholar 

  203. Todd MD, Lee MJ, Williams JL, Nalezny JM, Gee P, Benjamin MB, Farr SB (1995) Stress responses to DNA damaging agents in the human colon carcinoma cell line RKO. Fundam Appl Toxicol 28:118–128

    Article  CAS  Google Scholar 

  204. Hastwell PW, Chai LL, Roberts KJ, Webster TW, Harvey JS, Rees RW, Walmsley RM (2006) High-specificity and high-sensitivity genotoxicity assessment in a human cell line: validation of the GreenScreen HC GADD45a-GFP genotoxicity assay. Mutat Res 607:160–175

    Article  CAS  Google Scholar 

  205. Walmsley RM (2008) GADD45a-GFP GreenScreen HC genotoxicity screening assay. Expert Opin Drug Metab Toxicol 4:827–835

    Article  CAS  Google Scholar 

  206. Beard SE, Capaldi SR, Gee P (2009) Stress responses to DNA damaging agents in the human colon carcinoma cell line RKO. Mutat Res 371:1–13

    Google Scholar 

  207. O’Connell-Rodwell CE, Shriver D, Simanovskii DM, McClure C, Cao YA, Zhang W, Bachmann MH, Beckham JT, Jansen ED, Palanker D, Schwettman HA, Contag CH (2004) A genetic reporter of thermal stress defines physiologic zones over a defined temperature range. FASEB J 18:264–271

    Article  CAS  Google Scholar 

  208. Fischbach M, Sabbioni E, Bromley P (1993) Induction of the human growth hormone gene placed under human hsp70 promoter control in mouse cells: a quantitative indicator of metal toxicity. Cell Biol Toxicol 9:177–188

    Article  CAS  Google Scholar 

  209. Yoshizumi M, Wang H, Hsieh CM, Sibinga NE, Perrella MA, Lee ME (1997) Down-regulation of the cyclin A promoter by transforming growth factor-beta1 is associated with a reduction in phosphorylated activating transcription factor-1 and cyclic AMP-responsive element-binding protein. J Biol Chem 272:22259–22264

    Article  CAS  Google Scholar 

  210. Imreh G, Beckman M, Iverfeldt K, Hallberg E (1998) Noninvasive monitoring of apoptosis versus necrosis in a neuroblastoma cell line expressing a nuclear pore protein tagged with the green fluorescent protein. Exp Cell Res 238:371–376

    Article  CAS  Google Scholar 

  211. Mahajan NP, Harrison-Shostak DC, Michaux J, Herman B (1999) Novel mutant green fluorescent protein protease substrates reveal the activation of specific caspases during apoptosis. Chem Biol 6:401–409

    Article  CAS  Google Scholar 

  212. Strebel A, Harr T, Bachmann F, Wernli M, Erb P (2001) Green fluorescent protein as a novel tool to measure apoptosis and necrosis. Cytometry 43:126–133

    Article  CAS  Google Scholar 

  213. Johnson JM, Latimer JJ (2005) Analysis of DNA repair using transfection-based host cell reactivation. Methods Mol Biol 291:321–335

    CAS  Google Scholar 

  214. Stoklosa T, Poplawski T, Koptyra M, Nieborowska-Skorska M, Basak G, Slupianek A, Rayevskaya M, Seferynska I, Herrera L, Blasiak J, Skorski T (2008) BCR/ABL inhibits mismatch repair to protect from apoptosis and induce point mutations. Cancer Res 68:2576–2580

    Article  CAS  Google Scholar 

  215. Zhou B, Huang C, Yang J, Lu J, Dong Q, Sun LZ (2009) Preparation of heteroduplex EGFP plasmid for in vivo mismatch repair activity assay. Anal Biochem 388:167–169

    Article  CAS  Google Scholar 

  216. Roguev A, Russev G (2000) Two-wavelength fluorescence assay for DNA repair. Anal Biochem 287:313–318

    Article  CAS  Google Scholar 

  217. Collis SJ, Sangar VK, Tighe A, Roberts SA, Clarke NW, Hendry JH, Margison GP (2002) Development of a novel rapid assay to assess the fidelity of DNA double-strand-break repair in human tumour cells. Nucleic Acids Res 30:e1

    Article  CAS  Google Scholar 

  218. Slebos RJ, Taylor JA (2001) A novel host cell reactivation assay to assess homologous recombination capacity in human cancer cell lines. Biochem Biophys Res Commun 281:212–219

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Radiation Biology Department, Institute of Aerospace Medicine, German Aerospace Centre (DLR), Linder Hoehe, 51147, Cologne, Germany

    Christa Baumstark-Khan, Christine E. Hellweg & Günther Reitz

Authors
  1. Christa Baumstark-Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christine E. Hellweg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Günther Reitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christa Baumstark-Khan .

Editor information

Editors and Affiliations

  1. , Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 91904, Israel

    Shimshon Belkin

  2. , College of Life Sciences & Biotechnology, Korea University, Amam-dong 5-ga, Seoul, 136-701, Korea, Republic of (South Korea)

    Man Bock Gu

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer

About this chapter

Cite this chapter

Baumstark-Khan, C., Hellweg, C.E., Reitz, G. (2010). Cytotoxicity and Genotoxicity Reporter Systems Based on the Use of Mammalian Cells. In: Belkin, S., Gu, M. (eds) Whole Cell Sensing System II. Advances in Biochemical Engineering / Biotechnology, vol 118. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_2009_20

Download citation

Publish with us

Policies and ethics

Search

Navigation