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Mechanisms Leading to the Expression of Recessive Alleles: The Use of Polymorphic Microsatellites and Whole-Chromosome Painting Probes to Analyze Mouse Tumors, Mutants, and Micronuclei

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Book cover Risk and Progression Factors in Carcinogenesis

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 143))

Abstract

Regulatory agencies have the responsibility for assessing the potential risks that chemicals pose to humans. For risk assessment, these agencies evaluate data from in vitro genotoxicity assays (e.g., mutation induction using cells in culture) and from in vivo assays (e.g., micronucleus induction in bone marrow or carcinogenicity testing in rodents). The goal is to develop sensitive models that predict carcinogenic potential in susceptible human populations. Until recently, it was impossible to evaluate whether the genetic events induced by test compounds in the model systems were the same as the genetic events contributing to human cancers. However, new techniques make it possible to evaluate these events in both human and model systems and should aid in evaluating the appropriateness of any particular assay in predicting the disease in humans.

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References

  • Aaltonen LA, Peltomäki P, Leach FS, Sistonen P, Pylkkänen L, Mecklin J-P, Järvinen H, Powell S, Jen J, Hamilton SR, Petersen GM, Kinzler KW, Vogelstein B, de la Chapelle A (1993) Clues to the pathogenesis of familial colorectal cancer. Science 260: 812–816

    Article  PubMed  CAS  Google Scholar 

  • Ahn J, Lüdecke H-J, Lindow S, Horton WA, Lee B, Wagner MJ, Horsthemke B, Wells DE (1995) Cloning of the putative tumour suppressor gene for hereditary multiple exostoses (EXT 1), Nature Genet 11: 137–143

    Article  PubMed  CAS  Google Scholar 

  • Applegate ML, Moore MM, Broder CB, Burrell A, Juhn G, Kasweck KL, Lin PF, Wadhams A, Hozier JC (1990) Molecular dissection of mutations at the heterozygous thymidine kinase locus in mouse lymphoma cells. Proc Natl Acad Sci USA 87: 51–55

    Article  PubMed  CAS  Google Scholar 

  • Barrett J, Wiseman R (1987) Cellular and molecular mechanisms of multistep carcinogenesis: relevance to carcinogen risk assessment. Environ Health Perspect 76: 65–70

    Article  PubMed  CAS  Google Scholar 

  • Bishop J (1987) The molecular genetics of cancer. Science 235: 305–311

    Article  PubMed  CAS  Google Scholar 

  • Blazak W, Stewart B, Galperin I, Allen K, Rudd C, Mitchell A, Caspary W (1986a) Chromosome analysis of trifluorothymidine-resistant L5178Y mouse lymphoma cell colonies. Environ Mutagen 8: 229–240

    Article  PubMed  CAS  Google Scholar 

  • Blazak W, Stewart B, Galperin I, Allen K, Rudd C, Mitchell A, Caspary W (1986b) Stable dicentric chromosomes induced by chemical mutagens in L5178Y mouse lymphoma cells. Mutat Res 173: 263–266

    Article  PubMed  CAS  Google Scholar 

  • Blazak WF, Los FJ, Rudd CJ, Caspary WJ (1989) Chromosome analysis of small and large L5178Y mouse lymphoma cell colonies. Comparison of trifluorothymidine- resistant and unselected cell colonies from mutagen-treated and control cultures. Mutat Res 224: 197–208

    Article  PubMed  CAS  Google Scholar 

  • Boveri T (1914) Zur Frage der Entstehung maligner Tumoren. Fischer, Jena

    Google Scholar 

  • Breneman JW, Ramsey MJ, Lee DA, Eveleth GG, Minkler JL, Tucker JD (1993) The development of chromosome-specific composite DNA probes for the mouse and their application to chromosome painting. Chromosoma 102: 591–598

    Article  PubMed  CAS  Google Scholar 

  • Caspary W, Lee YJ, Poulton S, Myhr B, Mitchell A (1988a) Evaluation of the mouse L5178Y lymphoma system as an indicator of the mutagenic activity of chemicals: quality control criteria and response categories. Environ Mol Mutagen 12 [Suppl. 13]: 19–36

    PubMed  CAS  Google Scholar 

  • Caspary WJ, Myhr B, Mitchell A (1988b) Evaluation of the mouse L5178Y lymphoma system as an indicator of the mutagenic activity of chemicals: V. interlaboratory reproducibility and assessment. Environ Mol Mutagen 12: 195–229

    CAS  Google Scholar 

  • Cavenee W, Dryja T, Phillips R (1983) Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 205: 779–784

    Article  Google Scholar 

  • Cavenee W, Koufos A, Hansen M (1988) Recessive mutant genes predisposing to human cancer. Mutat Res 168: 3–14

    Google Scholar 

  • Clive D, Flamm WG, Machesko MR, Bernheim NJ (1972) Mutational assay system using the thymidine kinase locus in mouse lymphoma cells. Mutat Res 16: 77–87

    Article  PubMed  CAS  Google Scholar 

  • Clive D, Johnson K, Spector J, Batson A, Brown MM (1979) Validation and characterization of the L5178Y/tk mouse lymphoma mutagen assay system. Mutat Res 59: 61–108

    Article  PubMed  CAS  Google Scholar 

  • Clive D, Glover P, Applegate M, Hozier J (1990) Molecular aspects of chemical mutagenesis in L5178Y/tk +/− mouse lymphoma cells. Mutagenesis 5: 191–187

    Article  PubMed  CAS  Google Scholar 

  • Clive D, Glover P, Krehl R, Poorman-Allen P (1991) Mutagenicity of 2-amino-N6- hydroxyadenine (AHA) at three loci in L5178Y/tk +/− mouse lymphoma cells: molecular and preliminary cytogenetic characterizations of AHA-induced tk −/− mutants. Mutat Res 253: 73–82

    PubMed  CAS  Google Scholar 

  • Clontech (1995) Clontechniques X: 14–15

    Google Scholar 

  • Collins F (1995) Positional cloning moves from perditional to traditional. Nature Genet 9: 347–350

    Article  PubMed  CAS  Google Scholar 

  • Combes RD, Stopper H, Caspary WJ (1995) The use of L5178Y mouse lymphoma cells to assess mutagenic, clastogenic and aneugenic activity of chemicals. Mutagenesis (in press)

    Google Scholar 

  • Cremer T, Lichter P, Borden J, Ward DC, Manuelidis L (1988) Detection of chromosome aberrations in metaphase and interphase tumor cells by in situ hybridization using chromosome-specific library probes. Hum Gene 80: 235–246

    Article  CAS  Google Scholar 

  • Curtis LJ, Bubb VJ, Gledhill S, Morris RG, Bird CC, Wyllie AH (1994) Loss of heterozygosity of MCC is not associated with mutation of the retained allele in sproadic colorectal cancer. Hum Mol Genet 3: 443–446

    Article  PubMed  CAS  Google Scholar 

  • Davis LM, Caspary WJ, Sakallah SA, Maronpot R, Wiseman R, Barrett JC, Elliott R, Hozier JC (1994) Loss of heterozygosity in spontaneous and chemically induced liver tumors from the B6C3F1 mouse. Carcinogenesis 15: 1637–1645

    Article  PubMed  CAS  Google Scholar 

  • Dietrich W, Katz H, Lincoln SE, Shin H-S, Friedman J, Dracopoli NC, Lander ES (1992a) A genetic map of the mouse suitable for typing intraspecific crosses. Genetics 131: 423–447

    CAS  Google Scholar 

  • Dietrich W, Miller J, Katz H, Joyce D, Stean R, Lincoln S, Daly M, Reeve MP, Goodman N, Dracopoli N, Lander ES (1992b) SSLP microsatellite map. In:O’Brien SJ (ed) Genetic maps, nonhuman vertebrates, vol 4, 6th edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 110–142

    Google Scholar 

  • Ding SF, Habib NA, Dooley J, Wood C, Bowles L, Delhanty DA (1991) Loss of constitutional heterozygosity on chromosome 5q in hepatocellular carcinoma without cirrhosis. Br J Cancer 64 (6): 1083–1087

    Article  PubMed  CAS  Google Scholar 

  • Ding SF, Delhanty JDA, Dooley JS, Bowles L, Wood CB, Habib NA (1993) The putative tumor suppressor gene on chromosome 5q for hepatocellular carcinoma is distinct from the MCC and APC genes. Cancer Detect Prevention 17: 405–409

    CAS  Google Scholar 

  • Fenech M (1993) The cytokinesis-block micronucleus technique: a detailed description of the method and its application to genotoxicity studies in human populations. Mutat Res 285: 35–44

    Article  PubMed  CAS  Google Scholar 

  • Fritzenschaf H, Kohlpoth M, Rusche B, Schiífmann D (1993) Testing of known carcinogens and noncarcinogens in the Syrian hamster embryo (SHE) micronucleus test in vitro: correlation with in vivo micronucleus formation and cell transformation. Mutat Res 319: 47–53

    Article  PubMed  CAS  Google Scholar 

  • Gille JJ, van Berkel CG, Joenje H (1994) Mutagenicity of metabolic oxygen radicals in mammalian cell cultures. Carcinogenesis 15: 2695–2699

    Article  PubMed  CAS  Google Scholar 

  • Gray JW, Dean PN, Fuscoe JC, Peters DC, Trask BJ, van den Ength GJ (1987) High speed chromosome sorting. Science 238: 323–329

    Article  PubMed  CAS  Google Scholar 

  • Guan X-Y, Trent JM, Meitzer PS (1993) Generation of band-specific painting probes from a single microdissected chromosome. Hum Mol Genet 2: 1117–1121

    Article  PubMed  CAS  Google Scholar 

  • Guan X-Y, Meitzer PS, Trent J (1994) Rapid generation of whole chromosome painting probes ( WCPs) by chromosome microdissection. Genomics 22: 101–107

    Google Scholar 

  • Gudi R, Xu Y, Thilager A (1992) Assessment of the in vivo aneuploidy/micronucleus assay in mouse bone marrow cells with 16 chemicals. Environ Mol Mutagen 20: 106–116

    Article  PubMed  CAS  Google Scholar 

  • Hearne CM, McAleer MA, Love JM, Aitman TJ, Cornali RJ, Ghosh S, Knight AM, Prins JB, Todd JA (1991) Additional microsatellite markers for mouse genome mapping. Mammalian Genome 1: 273–282

    Article  PubMed  CAS  Google Scholar 

  • Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) P53 mutations in human cancers. Science 253: 49–53

    Article  PubMed  CAS  Google Scholar 

  • Hozier J, Sawyer J, Clive D, Moore M (1982) Cytogenetic distinction between the TK + and TK− chromosomes in the L5178Y TK +/− 3.7.2C mouse-lymphoma cell line. Mutat Res 105: 451–456

    Article  PubMed  CAS  Google Scholar 

  • Hozier J, Sawyer J, Clive D, Moore M (1982) Cytogenetic distinction between the TK + and TK− chromosomes in the L5178Y TK +/− 3.7.2C mouse-lymphoma cell line. Mutat Res 105: 451–456

    Article  PubMed  CAS  Google Scholar 

  • Hozier J, Sawyer J, Clive D, Moore MM (1985) Chromosome 11 aberrations in small colony L5178Y TK mutants early in their clonal history. Mutat Res 147: 237–242

    PubMed  CAS  Google Scholar 

  • Hozier J, Sawyer JR, Moore MM (1989) High-resolution cytogenetic analysis of L5178Y TK + − 3.7.2c cells: variation in chromosome 11 breakpoints among small-colony TK−/− mutants. Mutat Res 214: 195–199

    Article  PubMed  CAS  Google Scholar 

  • Hozier J, Scalzi J, Sawyer J, Carley N, Applegate M, Clive D, Moore M (1991) Localization of the mouse thymidine kinase gene to the distal portion of chromosome 11. Genomics 10: 827–832

    Article  PubMed  CAS  Google Scholar 

  • Hozier J, Applegate M, Moore MM (1992) In vitro mammalian mutagenesis as a model for genetic lesions in human cancer. Mutat Res 270: 201–209

    Article  PubMed  CAS  Google Scholar 

  • Hozier J, Graham R, Westfall T, Siebert P, Davis L (1994) Preparative in situ hybridization: selection of chromosome region-specific libraries on mitotic chromosomes. Genomics 19: 441–447

    Article  PubMed  CAS  Google Scholar 

  • Kinzler KW, Nilbert MC, Su L-K, Vogelstein B, Bryan TM, Levy DB, Smith KJ, Preisinger AC, Hedge P, McKechnie D, Finniear R, Markham A, Groffen J, Boguski MS, Altschul SF, Horii A, Ando H, Miyoshi Y, Miki Y, Nishisho I, Nakamura Y (1991) Identification of FAP locus genes from chromosome 5q21. Science 253: 661–664

    Article  PubMed  CAS  Google Scholar 

  • Knudson A (1985) Hereditary cancer, oncogenes and antioncogenes. Cancer Res 45: 1437–1443

    PubMed  CAS  Google Scholar 

  • Ledbetter SA, Nelson DL, Warren ST, Ledbetter D (1990) Rapid isolation of DNA probes within specific chromosome regions by interspersed repetitive sequence polymerase chain reaction. Genomics 6: 475–481

    Article  PubMed  CAS  Google Scholar 

  • Li CY, Yandell DW, Little JB (1992) Molecular mechanisms of spontaneous and induced loss of heterozygosity in human cells in vitro. Somat Cell Mol Genet 18: 77–87

    Article  PubMed  CAS  Google Scholar 

  • Lichter P, Cremer T, Borden J, Manuelidis L, Ward DC (1988a) Delineation of individual chromosomes in metaphase and interphase cells by in situ suppression hybridization using recombinant DNA libraries. Hum Genet 80: 224–234

    Article  PubMed  CAS  Google Scholar 

  • Lichter P, Cremer T, Tang CC, Watkins PC, Manuelidis L, Ward DC (1988b) Rapid detection of human chromosome 21 aberrations by in situ hybridization. Proc Natl Acad Sci USA 85: 9664–9668

    Article  PubMed  CAS  Google Scholar 

  • Liechty MC, Rauchfuss HS, Lugo MH, Hozier JC (1993) Sequence analysis of tka−−1 and tkb +-1 alleles in L5178Ytk +/ mouse-lymphoma cells and spontaneous tk−/− mutants. Mutat Res 286: 299–307

    Article  PubMed  CAS  Google Scholar 

  • Liechty MC, Hassanpour Z, Hozier JC, Clive D (1994) Use of microsatellite DNA polymorphisms on mouse chromosome 11 for in vitro analysis of thymidine kinase gene mutations. Mutagenesis 9: 423–427

    Article  PubMed  CAS  Google Scholar 

  • Liechty MC, Crosby H, Murthy A, Davis LM, Caspary WJ, Hozier JC (1995a) Identification of a polymorphic microsatellite within the tk gene in L5178Y mouse lymphoma cells. Nucleic Acids Res (in press)

    Google Scholar 

  • Liechty MC, Hall BK, Scalzi JM, Davis LM, Caspary WJ, Hozier JC (1995b) Mouse chromosome-specific painting probes generated from microdissected chromosomes. Mammal Genome (in press)

    Google Scholar 

  • Little JB (1989) In vitro models of carcinogenesis: expression of recessive genes by chromosomal mutations. Environ Health Perspect 81: 63–66

    Article  PubMed  CAS  Google Scholar 

  • Love JM, Knight AM, McAleer MS, Todd JA (1990) Towards construction of a high resolution map of the mouse genome using PCR-analysed microsatellites. Nucleic Acids Res 18: 4123–4130

    Article  PubMed  CAS  Google Scholar 

  • Matsuoka A, Yamasaki N, Suzuki T, Hayashi N, Sofuni T (1993) Evaluation of the micronucleus test using a Chinese hamster cell line as an alternative to the conventional in vitro chromosomal aberration test. Mutat Res 272: 223–236

    Google Scholar 

  • Meltzer PS, Guan X-Y, Burgess A, Trent JM (1992) Rapid generation of region specific probes by chromosome microdissection and their application. Nat Genet 1: 24–28

    Article  PubMed  CAS  Google Scholar 

  • Miller J (1992) Genetic map of the mouse. Whitehead Institute/MIT Center for Genome Research, Cambridge, MA

    Google Scholar 

  • Miyashita K, Voojis MA, Tucker JD, Lee DA, Gray JW, Pallavicini MG (1994) A mouse chromosome library generated from sorted chromosomes using linker-adapter polymerase chain reaction. Cytogenet Cell Genet 66: 54–57

    Article  PubMed  CAS  Google Scholar 

  • Montagutelli X, Serikawa T, Guenet J (1991) PCR-analysed microsatellites: data concerning laboratory and wild-derived mouse inbred strains. Mammal Genome 11: 225–259

    Google Scholar 

  • Nakamura Y, Leppert M, O’Connell P, Wolff R, Holm T, Culver M, Martin C, Fujimoto E, Hoff M, Kumlin E, White R (1987) Variable number of tandem repeat ( VNTR) markers for human gene mapping. Science 235: 1616–1622

    Article  PubMed  CAS  Google Scholar 

  • Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsu-nomiya J, Baba S, Hedge P, Markham A, Krush AJ, Petersen G, Hamilton SR, Nilbert MC, Levy DB, Bryan TM, Preisinger AC, Smith KJ, Su L-K, Kinzier KW, Vogelstein B (1991) Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253: 665–669

    Article  PubMed  CAS  Google Scholar 

  • Rudd C, Daston D, Caspary WJ (1990) Spontaneous mutation rates in mammalian cells: effect of differential growth rates and phenotypic lag. Genetics 126: 435–442

    PubMed  CAS  Google Scholar 

  • Smith LE, Grosovsky AJ (1993) Genetic instability on chromosome 16 in a human B lymphoblastoid cell line. Somat Cell Mol Genet 19: 515–527

    Article  PubMed  CAS  Google Scholar 

  • Spencer DL, Caspary WJ (1994) In situ and suspension protocols for mutation in L5178Y mouse cells: dose response and colony size distribution, Mutat Res 322: 291–300

    Article  Google Scholar 

  • Spencer DL, Hines KC, Caspary WJ (1994) An in situ protocol for measuring the expression of chemically induced mutations in mammalian cells. Mutat Res. 312: 85–98

    PubMed  CAS  Google Scholar 

  • Stanbridge EJ (1992) Functional evidence for human tumor suppressor genes: chromosome and molecular genetic studies. Cancer Surv 12: 5–24

    PubMed  CAS  Google Scholar 

  • Stopper H, Körber C, Schiffmann D, Caspary WJ (1993a) Cell cycle dependent mi-cronucleus formation and mitotic disturbances in mammalian cells treated with 5-azacytidine. Mutat Res 300: 165–177

    Article  PubMed  CAS  Google Scholar 

  • Stopper H, Körber C, Spencer DL, Kirchner S, Caspary WJ, Schiffmann D (1993b) An investigation of micronucleus and mutation induction by oxazepam in mammalian cells. Mutagenesis 8: 449–455

    Article  PubMed  CAS  Google Scholar 

  • Stopper H, Eckert I, Schiffmann D, Spencer D, Caspary WJ (1994) Is micronucleus induction by aneugens an early event in mutagenesis? Mutagenesis 9: 411–416

    Article  PubMed  CAS  Google Scholar 

  • Stopper H, Diener U, Schwefel I, Bittner D (1995) Does the presence of a fragile site lead to micronucleus formation? J Cancer Clin One 121 (2): M26

    Google Scholar 

  • Tautz D (1989) Hypervariability of simple sequences as a general source for polymorphic DNA markers. Nucleic Acids Res 17: 6463–6471

    Article  PubMed  CAS  Google Scholar 

  • Telenius H, de Vos D, Blennow E, Willat LR, Ponder BA, Carter NP (1993) Chromatid contamination can impair the purity of flow-sorted metaphase chromosomes. Cytometry 14: 97–101

    Article  PubMed  CAS  Google Scholar 

  • Tennant R, Margolin B, Shelby M, Zeiger E, Haseman J, Spalding J, Caspary W, Resnick M, Stasiewicz S, Anderson B, Minor R (1987) Prediction of chemical carcinogenicity in rodents from in vitro genetic toxicity assays. Science 236: 933–941

    Article  PubMed  CAS  Google Scholar 

  • Thibodeau SN, Bren G, Schald D (1993) Microsatellite instability in cancer of the proximal colon. Science 260: 815–819

    Article  Google Scholar 

  • Weber JL, May PE (1989) Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet 44: 388–396

    PubMed  CAS  Google Scholar 

  • Weinberg RA (1991) Tumor suppressor genes. Science 254: 1138–1146

    Google Scholar 

  • Weier HUG, Polikoff D, Fawcett JJ, Greulich KM, Lee KH, Cram S, Chapman VM, Gray JW (1994) Generation of five high-complexity painting probe libraries from flowsorted mouse chromosomes. Genomics 21: 641–644

    Article  PubMed  CAS  Google Scholar 

  • Xia F, Amundson SA, Nickoloff JA, Liber HL (1994) Different capacities for recombination in closely related human lymphoblastoid cell lines with different mutational responses to X-irradiation. Mol Cell Biol 14: 5850–5857

    PubMed  CAS  Google Scholar 

  • Zhang J, Meitzer P, Jenkins R, Guan X-Y, Trent J (1993) Application of chromosome microdissection probes for elucidation of BCR-ABL fusion and variant Philadelphia chromosome translocation in chronic myelogenous leukemia. Blood 81: 3365–3371

    PubMed  CAS  Google Scholar 

  • Zhu Y, Stambrook PJ, Tischfield JA (1993) Loss of heterozygosity: the most frequent cause of recessive phenotype expression at the heterozygous human adenine phosphoribosyltransferase locus. Mol Carcinogen 8: 138–144

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institutes of Health, Research Triangle Park, NC, 27709, USA

    W. J. Caspary

  2. Department of Toxicology, University of Würzburg, 97078, Würzburg, Germany

    H. Stopper

  3. Applied Genetics Laboratories, 1335 Gateway Drive, Suite 2001, Melbourne, FL, 32901, USA

    J. C. Hozier, M. C. Liechty & L. M. Davis

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  1. W. J. Caspary
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  2. H. Stopper
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  3. J. C. Hozier
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  4. M. C. Liechty
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  5. L. M. Davis
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Editors and Affiliations

  1. Pathologisches Institut, der Universität Würzburg, Josef-Schneider-Straße 2, 97080, Würzburg, Germany

    H. K. Müller-Hermelink

  2. Institut für Pharmakologie und Toxikologie, der Universität Würzburg, Versbacher Straße 9, 97078, Würzburg, Germany

    H.-G. Neumann  & W. Dekant  & 

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Caspary, W.J., Stopper, H., Hozier, J.C., Liechty, M.C., Davis, L.M. (1997). Mechanisms Leading to the Expression of Recessive Alleles: The Use of Polymorphic Microsatellites and Whole-Chromosome Painting Probes to Analyze Mouse Tumors, Mutants, and Micronuclei. In: Müller-Hermelink, H.K., Neumann, HG., Dekant, W. (eds) Risk and Progression Factors in Carcinogenesis. Recent Results in Cancer Research, vol 143. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60393-8_11

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  • DOI: https://doi.org/10.1007/978-3-642-60393-8_11

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