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The Contribution of DNA Methylation to the Generation of Tumor Cell Heterogeneity, Tumor Progression and Metastasis

  • Chapter
Influence of Tumor Development on the Host

Part of the book series: Cancer Growth and Progression ((CAGP,volume 3))

Abstract

The ability of neoplastic cells to form metastatic deposits at points far removed from the location of a primary tumor represents one of the most complex processes associated with cancer cell biology. Clinically, metastasis accounts in large part, for the lethal aspect of the disease. It has now become widely recognized that in order for a tumor cell to be able to complete all of the steps in the metastatic process, it must be endowed with or express a spectrum of pheno-types (75). Since the pioneering studies of Fidler and his colleagues (26), most studies have shown or implied that only a very small minority of the neoplastic cells within a tumor may possess all of the biological properties which are necessary in order for metastasis to take place. This heterogeneity in the tumor cell population is not limited to metastatic ability, but also extends to a number of other cellular properties ranging from growth rate to drug sensitivity (38). Moreover, this heterogeneity in cellular phenotypes is not only found within primary tumors, but may also develop within and between individual metastatic lesions (76, 94).

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References

  1. Adams RLP, Burdon, RH: DNA Methylases. In: Enzymes of Nucleic Acid Synthesis and Modification, Volume I, edited by ST Jacob, CRC Press, Inc, Boca Raton, Fla, 1983 pp 119–144

    Google Scholar 

  2. Agarwal RP, Spector T, Parks RE: Tight binding inhibitors IV. Inhibition of adenosine deaminases by various inhibitors. Biochem Pharm 26:359, 1977

    PubMed  CAS  Google Scholar 

  3. Banerjee A, Benedict WF: Production of sister chromatid exchanges by various cancer chemotherapeutic agents. Cancer Re 39:797, 1979

    CAS  Google Scholar 

  4. Bartel RL, Borchardt RT: Effects of adenosine dialdehyde on S-adenosylhomocysteine hydrolase and S-adenosylmethio-nine-dependent transmethylations in mouse L929 cells. Mol Pharm 25:418, 1984

    CAS  Google Scholar 

  5. Benvenisty N, Szyf M, Mencher D, Razin A, Reshef L: Tissue-specific hypomethylation and expression of rat phos-phoenolpyruvate carboxykinase gene induced by in vivo treatment of fetuses and neonates with 5-azacytidine. Biochem 24:5015, 1985

    CAS  Google Scholar 

  6. Boehm TLJ, Drahovsky D: Hypomethylation of DNA in Raji cells after treatment with N-methyl-N-nitrosurea. Carcinogen 2:39, 1981

    CAS  Google Scholar 

  7. Boehm TLJ, Drahovsky D: Elevated level of enzymatic DNA methylation in cells treated with l-β-D-arabinofuranosyl-cytosine, Cancer Res 42:1537, 1982

    PubMed  CAS  Google Scholar 

  8. Boehm TLJ, Drahovsky D: Alteration of enzymatic methylation of DNA cytosines by chemical carcinogens: A mechanism involved in the initiation of carcinogenesis. J Natl Cancer Inst 71:429, 1983

    PubMed  CAS  Google Scholar 

  9. Boehm TLJ, Drahovsky D: DNA hypermethylation and changes in gene expression may be related to the chemotherapeutic action of cytarabin. Eur J Cancer Clin Oncol 20:-1561, 1984

    PubMed  CAS  Google Scholar 

  10. Bouck N, Kokkinakis D, Ostrowsky J: Induction of a step in carcinogenesis that is normally associated with mutagenesis by nonmutagenic concentrations of 5-azacytidine. Mol Cell Biol 4:1231, 1984

    PubMed  CAS  Google Scholar 

  11. Carlow DA, Kerbel RS, Feltis JT, Elliott BE: Enhanced expression of class I major histocompatibility complex gene (Dk) products on immunogenic variants of a spontaneous murine carcinoma. J Natl Cancer Inst 75:291, 1985

    PubMed  CAS  Google Scholar 

  12. Chabot GG, Momparler RL: Antileukemic activity of 5-aza-2′-deoxycytidine and cytarabine against intracerebral L1210 murine leukemia. Cancer Treatment Reports 68:1483, 1984

    PubMed  CAS  Google Scholar 

  13. Cheah MSC, Wallace CD, Hoffman RM: Hypomethylation of DNA in human cancer cells: A site-specific change in the c-myc oncogene. J Natl Cancer Inst 73:1057, 1984

    PubMed  CAS  Google Scholar 

  14. Christman JK, Mendelsohn N, Herzog D, Schneiderman N: Effect of 5-azacytidine on differentiation and DNA methylation in human promyelocytic leukemia cells (HL-60). Cancer Res 43:763, 1983

    PubMed  CAS  Google Scholar 

  15. Cook JR, Chiu J: Effect of 5-azacytidine on rat liver alpha-fetoprotein gene expression. Biochem Biophys Res Comm 116:939, 1983

    PubMed  CAS  Google Scholar 

  16. Cooper DN: Eukaryotic DNA methylation. Hum Genet 64:315, 1983

    PubMed  CAS  Google Scholar 

  17. Covey JM, Zaharko DS: Comparison of the in vitro cytotoxicity (LI210) of 5-aza-2′-deoxycytidine with its therapeutic and toxic effects in mice. Eur J Cancer Clin Oncol 21:109, 1985

    PubMed  CAS  Google Scholar 

  18. Cremisi C: Effect of 5-azacytidine treatment on mouse embryonal carcinoma cells. J Cell Physiol 116:181, 1983

    PubMed  CAS  Google Scholar 

  19. Creusot F, Acs G, Christman JK: Inhibition of DNA methyl-ferase and induction of friend erythroleukemia cell differentiation by 5-azacytidine and 5-aza-2′-deoxycytidine. J Biol Chem 257:2041, 1982

    PubMed  CAS  Google Scholar 

  20. Darmon M, Nicolas J, Lamblin D: 5-Azacytidine is able to induce the conversion of teratocarcinoma-derived mesenchymal cells into epithelial cells. EMBO J 3:961, 1984

    PubMed  CAS  Google Scholar 

  21. Diala ES, Cheah MSC, Rowitch D, Hoffman RM: Extent of DNA methylation in human tumor cells. J Natl Cancer Inst 71:755, 1983

    PubMed  CAS  Google Scholar 

  22. Farrance IK, Ivarie R: Ethylation of poly(dC-dG)’ poly(dC-dG) by ethyl methanesulfonate stimulates the activity of mammalian DNA methyltransferase in vitro. Proc Natl Acad Sci USA 82:1045, 1985

    PubMed  CAS  Google Scholar 

  23. Feinberg AP, Vogelstein B: Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301:89, 1983

    PubMed  CAS  Google Scholar 

  24. Feinberg AP, Vogelstein B: Hypomethylation of ras oncogenes in primary human cancers. Biochem Biophys Res Comm 111:47, 1983

    PubMed  CAS  Google Scholar 

  25. Fialkow PJ: Clonal origin of human tumors. Annu Rev Med 30:135, 1979

    PubMed  CAS  Google Scholar 

  26. Fidler FJ, Kripke ML: Metastasis results from pre-existing variant cells within a malignant tumor. Science 197:893,1977

    PubMed  CAS  Google Scholar 

  27. Flatau E, Bogenmann E, Jones PA: Variable 5-methylcy-tosine levels in human tumor cell lines and fresh pediatric tumor expiants. Cancer Res 43:4091, 1983

    Google Scholar 

  28. Frost P, Kerbel RS: On a possible epigenetic mechanism(s) of tumor cell heterogeneity. Cancer Metastasis Rev 2:375, 1983

    PubMed  CAS  Google Scholar 

  29. Frost P, Liteplo RG, Donaghue TP, Kerbel RS: Selection of strongly immunogenic ‘Turn-’variants from tumors at high frequency using 5-azacytidine. J Exp Med 159:1491, 1984

    PubMed  CAS  Google Scholar 

  30. Foulds L: Neoplastic development Academic Press, New York, 1975

    Google Scholar 

  31. Gama-Sosa MA, Slagel VA, Trewyn RW, Oxenhandler R, Kuo KC, Gehrke CW, Ehrlich M: The 5-methylcytosine content of DNA from human tumors. Nucl Acids Res 11:6883, 1983

    PubMed  CAS  Google Scholar 

  32. Ginder GD, Whitters MJ, Pohlman JK: Activation of a chicken embryonic globin gene in adult erythroid cells by 5-azacytidine and sodium butyrate. Proc Natl Acad Sci USA 81:3954, 1984

    PubMed  CAS  Google Scholar 

  33. Goelz SE, Vogelstein B, Hamilton SR, Feinberg AP: Hypomethylation of DNA from benign and malignant human colon neoplasms. Science 228:187, 1985

    PubMed  CAS  Google Scholar 

  34. Gruenbaum Y, Szyf M, Cedar H, Razin A: Methylation of replicating and post-replicated mouse L-cell DNA. Proc Natl Acad Sci USA 80:4919, 1983

    PubMed  CAS  Google Scholar 

  35. Gupta RS, Singh B: Mutagenic responses of five independent genetic loci in CHO cells to a variety of mutagens. Development and characteristics of a mutagen screening system based on selection for multiple drug-resistance markers. Mutat Res 94:449, 1982

    PubMed  CAS  Google Scholar 

  36. Harris M: Induction of thymidine kinase in enzyme-deficient Chinese hamster cells. Cell 29:483, 1982

    PubMed  CAS  Google Scholar 

  37. Harrison J J, Anisowicz A, Gadi IK, Raffeld M, Sager R: Azacytidine-induced tumorigenesis of CHEF/18 cells: Correlated DNA methylation and chromosome changes. Proc Natl Acad Sci USA 80:6606, 1983

    PubMed  CAS  Google Scholar 

  38. Heppner GH: Tumor heterogeneity. Cancer Res 44:2259, 1984

    PubMed  CAS  Google Scholar 

  39. Hershfield MS, Kurtzberg J, Harden E, Moore JO, Whang-Peng J, Haynes BF: Conversion of a stem cell leukemia from a T-lymphoid to a myeloid phenotype induced by the adenosine deaminase inhibitor 2′-deoxycoformycin. Proc Natl Acad Sci USA 81:253, 1984

    PubMed  CAS  Google Scholar 

  40. Hoffman JL: Inhibition of S-adenosyl sulfur amino acid metabolism: Periodate-oxidized nucleosides as potent inhibitors of S-adenosylhomocysteine hydrolase. In: Transmethylation edited by Usdin E, Borchardt RT, Creveling CR, Elsevier, North Holland, Inc, New York, 1979, pp. 181–186

    Google Scholar 

  41. Hoffman JL: The rate of transmethylation in mouse liver as measured by trapping S-adenosylhomocysteine. Arch Biochem Biophys 205:132, 1980

    PubMed  CAS  Google Scholar 

  42. Hoffman RM: Altered methionine metabolism, DNA methylation and oncogene expression in carcinogenesis. Biochim Biophys Acta 738:49, 1984

    PubMed  CAS  Google Scholar 

  43. Holliday R: A new theory of carcinogenesis. Br J Cancer 40:513, 1979

    PubMed  CAS  Google Scholar 

  44. Hori T: Induction of chromosome decondensation, sister-chromatid exchanges and endoreduplications by 5-azacy-tidine, an inhibitor of DNA methylation. Mutat Res 121:47, 1983

    PubMed  CAS  Google Scholar 

  45. Hsiao W-LW, Gattoni-Celli S, Weinstein IB: Effects of 5-azacytidine on the progressive nature of cell transformation. Mol Cell Biol 5:1800, 1985

    PubMed  CAS  Google Scholar 

  46. Jaenisch R, Schnieke A, Harbers K: Treatment of mice with 5-azacytidine efficiently activates silent retroviral genomes in different tissues. Proc Natl Acad Sci USA 82:1451, 1985

    PubMed  CAS  Google Scholar 

  47. Jones PA, Taylor SM: Cellular differentiation, cytidine analogs and DNA methylation. Cell 20:85, 1980

    PubMed  CAS  Google Scholar 

  48. Jones PA, Taylor SM, Wilson VL: Inhibition of DNA methylation by 5-azacytidine. Recent Results in Cancer Research 84:202, 1983

    PubMed  CAS  Google Scholar 

  49. Jones PA: Effects of 5-azacytidine and its 2′-deoxyderivative on cell differentiation and DNA methylation. Pharmac Ther 28:17, 1985

    CAS  Google Scholar 

  50. Kastan MB, Gowans BJ, Lieberman MW: Methylation of deoxycytidine incorporated by excision-repair synthesis of DNA. Cell 30:509, 1982

    PubMed  CAS  Google Scholar 

  51. Kerbel RS, Davies AJS: Facilitation of tumour progression by cancer therapy. Lancet 11:977, 1982

    Google Scholar 

  52. Kerbel RS, Frost P, Liteplo R., Carlow DA, Elliott BE: Possible epigenetic mechanisms of tumor progression: Induction of high-frequency heritable but phenotypically unstable changes in the tumorigenic and metastatic properties of tumor cell populations by 5-azacytidine treatment. J Cell Physiol Suppl 3:87, 1984

    PubMed  CAS  Google Scholar 

  53. Koeffler HP: Induction of differentiation of human acute myelogenous leukemia cells: Therapeutic implications. Blood 62:709, 1983

    PubMed  CAS  Google Scholar 

  54. Landolph JR, Jones PA: Mutagenicity of 5-azacytidine and related nucleosides in C3H/10T1/2 Clone 8 and V79 cells. Cancer Res 42:817, 1982

    PubMed  CAS  Google Scholar 

  55. Lapeyre JN, Becker FF: 5-Methylcytosine content of nuclear DNA during chemical hepatocarcinogenesis and the carcinomas which result. Biochem Biophys Res Comm 87:698, 1979

    PubMed  CAS  Google Scholar 

  56. Lapeyre JN, Ruchirawat M, Becker FF: Current research on eukaryotic DNA methyltransferases. In: Progress in Nonhistone Protein Research Vol I, edited by Bekhor I, CRC Press, Boca Raton, Fla, 1985, pp. 167–190

    Google Scholar 

  57. Ley TL, DeSimone J, Anagnous NP, Keller GH, Humphries RK, Turner PH, Young NS, Heller P, Nienhuis AW: 5-Aza-cytidine selectively increases y-globin synthesis in a patient with β +-thalassemia. New Eng J Med 307:1467, 1982

    Google Scholar 

  58. Ley TL, DeSimone J, Noguchi CT, Turner PH, Scheckter AN, Heller P, Nienhius AW: 5-Azacytidine increases γ-globin synthesis and reduces the proportion of dense cells in patients with sickle cell anemia. Blood 62:370, 1983

    PubMed  CAS  Google Scholar 

  59. Liteplo RG, Kerbel RS: Reduced levels of DNA 5-methylcy-tosine in metastatic variants of the human melanoma cell line MeWo. Cancer Res 47:2264, 1987

    PubMed  CAS  Google Scholar 

  60. Liteplo RG, Frost P, Kerbel RS: 5-Azacytidine induction of thymidine kinase in a spontaneously enzyme-deficient murine tumor line. Exp Cell Res 150:499, 1984

    PubMed  CAS  Google Scholar 

  61. Liteplo RG, Alvarez E, Frost P, Kerbel RS: Induction of thymidine kinase activity in a spontaneously enzyme-deficient murine tumor cell line by exposure in vivo to the DNA-hypomethylating agent 5-Aza-2′-deoxycytidine: Implications for mechanisms of tumor progression. Cancer Res 45:5294, 1985

    PubMed  CAS  Google Scholar 

  62. Liteplo RG, Kerbel RS: Periodate-oxidized adenosine induction of murine thymidine kinase: The role of DNA methylation in the generation of tumor cell heterogeneity. Cancer Res 46:577, 1986

    PubMed  CAS  Google Scholar 

  63. Mohandas T, Sparkes RS, Bishop DF, Desnick RJ, Shapiro LJ: Frequency of reactivation and variability in expression of X-linked enzyme loci. Am J Hum Genet 36:916, 1984

    PubMed  CAS  Google Scholar 

  64. Momparler RL, Bouchard J, Onetto N, Rivard GE: 5-Aza-2′-deoxycytidine therapy in patients with acute leukemia inhibits DNA methylation. Leuk Res 8:181, 1984a

    PubMed  CAS  Google Scholar 

  65. Momparler RL, Momparler LF, Samson J: Comparison of the antileukemic activity of 5-aza-2’-deoxycytidine. 1-β-D-arabinofuranosylcytosine and 5-azacytidine against LI210 leukemia. Leuk Res 8:1043, 1984b

    PubMed  CAS  Google Scholar 

  66. Murphy SB, Stass S, Kalwensky D, Riviera G: Phenotypic conversion of acute leukemia from T-lymphoblastic to myeloblasts induced by therapy with 2′-deoxycoformycin. Br J Haematol 55:285, 1983

    PubMed  CAS  Google Scholar 

  67. Nicolson GL: Generation of phenotypic diversity and progression in metastatic tumor cells. Cancer Metastasis Rev 3:25, 1984

    PubMed  CAS  Google Scholar 

  68. Nowell PC: The clonal evolution of tumor cell populations. Science 194:23, 1976

    PubMed  CAS  Google Scholar 

  69. Nowell PC: Tumor progression and clonal evolution: The role of genetic instability. In: Chromosome Mutation and Neoplasia edited by German J, Alan R Liss Inc, New York, 1983, pp 413–432

    Google Scholar 

  70. Nyce J, Weinhouse S, Magee PN: 5-Methylcytosine depletion during tumour development: An extension of the miscoding concept. Br J Cancer 48:463, 1983

    PubMed  CAS  Google Scholar 

  71. Olsson L, Forchhammer J: Induction of the metastatic phenotype in a mouse tumor model by 5-azacytidine, and characterization of an antigen associated with metastatic activity. Proc Natl Acad Sci USA 81:3389, 1984

    PubMed  CAS  Google Scholar 

  72. Olsson L, Behnke O, Sorensen HR: Modulatory effects of 5-azacytidine, phorbol ester, and retinoic acid on the malignant phenotype of human lung cancer cells. Int J Cancer 35:189, 1985

    PubMed  CAS  Google Scholar 

  73. Ormerod EJ, Everett CA, Finch M, Hart IR: DNA methylation levels in human and murine melanoma cell lines of varying metastatic potential. Cancer Res 46:4342, 1986

    PubMed  CAS  Google Scholar 

  74. Ormerod EJ, Everett CA, Hart IR: Enhanced experimental metastatic capacity of a human tumor line following treatment with 5-azacytidine. Cancer Res 46:884, 1986

    PubMed  CAS  Google Scholar 

  75. Patel-Thombre U, Borchardt RT: Adenine nucleoside dial-dehydes: Potent inhibitors of bovine liver S-adenosylho-mocysteine hydrolase. Biochem 24:1130, 1985

    CAS  Google Scholar 

  76. Pfeifer GP, Grunwald S, Boehm TLJ, Drahovsky D: Isolation and characterisation of DNA cytosine 5-methyltrans-ferase from human placenta. Biochim Biophys Acta 740:323, 1983

    PubMed  CAS  Google Scholar 

  77. Poste G, Fidler IJ: The pathogenesis of cancer metastasis. Nature 283:139, 1980

    PubMed  CAS  Google Scholar 

  78. Poste G, Tzeng J, Doll J, Greig R, Rieman D, Zeidman I: Evolution of tumor cell heterogeneity during progressive growth of individual lung metastases. Proc Natl Acad Sci USA 19:6514, 1982

    Google Scholar 

  79. Poupon M, Pauwels C, Jasmin C, Antoine E, Lascaus V, Rosa B: Amplified pulmonary metastases of a rat rhabdomyosarcoma in response to nitrosourea treatment. Cancer Treatment Reports 68:749, 1984

    PubMed  CAS  Google Scholar 

  80. Ramsden M, Cole G, Smith J, Balmain A: Differential methylation of the c-H-ras gene in normal mouse cells and during skin tumour progression. EMBO 7 4:1449, 1985

    Google Scholar 

  81. Razin A, Riggs AD: DNA methylation and gene function. Science 210:604, 1980

    PubMed  CAS  Google Scholar 

  82. Razin A, Szyf M: DNA methylation patterns. Formation and function. Biochim Biophys Acta 782:331, 1984

    PubMed  CAS  Google Scholar 

  83. Razin A, Cedar H, Riggs A: DNA Methylation Biochemistry and Biological Significance. Springer-Verlag, New York, 1984

    Google Scholar 

  84. Riggs AD, Jones PA: 5-Methylcytosine, gene regulation and cancer. Cancer Res 40:1, 1983

    CAS  Google Scholar 

  85. Rivard GE, Momparler RL, Demers J, Benoit P, Raymond R, Lin K, Momparler LF: Phase I study on 5-aza-2′-deoxycytidine in children with acute leukemia. Leuk Res 5:453, 1981

    PubMed  CAS  Google Scholar 

  86. Sager R: The role of genomic rearrangements in tumor cell heterogeneity. In: Tumor Cell Heterogeneity Origins and Implications edited by Owens AH, Coffey DS, Baylin SB, Academic Press, New York, 1982, pp 411–422

    Google Scholar 

  87. Sartorelli AC: Malignant cell differentiation as a potential therapeutic approach. Br J Cancer 52:293, 1985

    PubMed  CAS  Google Scholar 

  88. Scarpa S, Strom R, Bozzi A, Aksamit RR, Backlund PS Jr, Chen J, Cantoni GL: Differentiation of myoblast cell lines and biological methylation: 3-Deazaadenosine stimulates formation of multinucleated myofibers. Proc Natl Acad Sci USA 81:3064, 1984

    PubMed  CAS  Google Scholar 

  89. Schimke RT: Gene amplification in cultured animal cells. Cell 37:705, 1984

    PubMed  CAS  Google Scholar 

  90. Schimke RT, Hill A, Johnston RN: Methotrexate resistance and gene amplification: an experimental model for the generation of cellular heterogeneity. Br J Cancer 51:459, 1985

    PubMed  CAS  Google Scholar 

  91. Shipley J, Sakai K, Tantravahi U, Fendrock B, Latt SA: Correspondence between effects of 5-azacytidine on SCE formation, cell cycling and DNA methylation in Chinese hamster cells. Mutat Res 150:333, 1985

    PubMed  CAS  Google Scholar 

  92. Shmookler Reis RJ, Goldstein S: Variability of DNA methylation patterns during serial passage of human diploid fibroblasts. Proc Natl Acad Sei USA 79:3949, 1982

    CAS  Google Scholar 

  93. Smith SS, Yu JC, Chen CW: Different levels of DNA modification at 5′CCGG in murine erythroleukemia cells and the tissues of normal mouse spleen. Nucl Acids Res 10:4305,1982

    PubMed  CAS  Google Scholar 

  94. Stern PH, Hoffman RM: Elevated overall rates of transmethylation in cell lines from diverse human tumors. In Vitro 20:663, 1984

    PubMed  CAS  Google Scholar 

  95. Szyf M, Avraham-Haetzni K, Reifman A, Shlomai J, Kaplan F, Oppenheim A, Razin A: DNA methylation pattern is determined by the intracellular level of the methylase. Proc Natl Acad Sci USA 81:3278, 1984

    PubMed  CAS  Google Scholar 

  96. Talmadge JE, Benedict K, Madsen J, Fidler IJ: Development of biological diversity and susceptibility to chemotherapy in murine cancer metastases. Cancer Res 44:3801, 1984

    PubMed  CAS  Google Scholar 

  97. Taylor SM, Constantinides PA, Jones PA: 5-Azacytidine, DNA methylation, and differentiation. Current Topics in Microbiology and Immunology 108:115, 1984

    PubMed  CAS  Google Scholar 

  98. Trainer DL, Kline T, Mallon F, Greig R, Poste G: Effect of 5-azacytidine on DNA methylation and the malignant properties of B16 melanoma cells. Cancer Res 45:6124, 1985

    PubMed  CAS  Google Scholar 

  99. Walker C, Ranney DF, Shay JW: 5-Azacytidine-induced uncoupling of differentiation and tumorigenicity in a murine cell line. J Natl Cancer Inst 73:877, 1984

    PubMed  CAS  Google Scholar 

  100. Wigler M, Levy D, Perucho M: The somatic replication of DNA methylation. Cell 24:33, 1981

    PubMed  CAS  Google Scholar 

  101. Wilson VL, Jones PA: Inhibition of DNA methylation by chemical carcinogens in vitro. Cell 32:239, 1983

    PubMed  CAS  Google Scholar 

  102. Wilson VL, Jones PA, Momparler RL: Inhibition of DNA methylation in LI210 leukemic cells by 5-aza-2′-deoxycy-tidine as a possible mechanism of chemotherapeutic action. Cancer Res 43:3493, 1983

    PubMed  CAS  Google Scholar 

  103. Woodcock DM, Crowther PU, Hunter SD, Cooper IA: DNA sequences showing a delay in cytosine methylation after replication. Time course of methylation in synchronized mammalian cell populations and relationship to DNAase I sensitive domains. Biochim Biophys Acta 741:38, 1983

    PubMed  CAS  Google Scholar 

  104. Zaharko DS, Covey JM: Effects of 5-aza-2′-deoxycytidine in combination with the biochemical modulator thymidine or the immune modulator pyran copolymer on L1210 leukemia-bearing mice. Cancer Treatment Reports 68:1255, 1984

    PubMed  CAS  Google Scholar 

  105. Zaharko DS, Covey JM, Muneses CC: Experimental chemotherapy (LI210) with 5-aza-2′-deoxycytidine in combination with pyran copolymer (MVE-4), an immune adjuvant. J Natl Cancer Inst 74:1319, 1985

    PubMed  CAS  Google Scholar 

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  1. Robert G. Liteplo
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  2. Robert S. Kerbel
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  3. Philip Frost
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  1. Department of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Md., USA

    Lance A. Liotta

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Liteplo, R.G., Kerbel, R.S., Frost, P. (1989). The Contribution of DNA Methylation to the Generation of Tumor Cell Heterogeneity, Tumor Progression and Metastasis. In: Liotta, L.A. (eds) Influence of Tumor Development on the Host. Cancer Growth and Progression, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-2528-1_11

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  • DOI: https://doi.org/10.1007/978-94-009-2528-1_11

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