Diversity of DNA topoisomerases I and inhibitors

Biochimie

Volumn 80, Issue 3, 1998, Pages 255-270

  Pommier, Y ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Cancer cells; DNA topoisomerase I; Topoisomerase inhibitors

Indexed keywords

5,6 DIHYDRO 2,3 DIMETHOXY 6 METHYL 8,9 METHYLENEDIOXY 5,11 DIOXO 11H INDENO[1,2 C]ISOQUINOLINE; 6 FORMYLAMINO 12,13 DIHYDRO 1,11 DIHYDROXY 5H INDOLO[2,3 A][PYRROLO[3,4 C]CARBAZOLE 5,7(6H) DIONE 13 GLUCOSIDE; 7 ETHYL 10 HYDROXYCAMPTOTHECIN; ANTHRACYCLINE; ANTINEOPLASTIC AGENT; BE 13793C; BENZIMIDAZOLE; BENZOPHENANTHRIDINE DERIVATIVE; BENZ[A]ANTHRACENE; CAMPTOTHECIN; CAMPTOTHECIN DERIVATIVE; CARBAZOLE DERIVATIVE; CORALYNE; DNA; DNA TOPOISOMERASE; DNA TOPOISOMERASE INHIBITOR; ED 110; FAGARONINE; INDOLOQUINOLINE DERIVATIVE; INTOPLICINE; IRINOTECAN; K 252A; KT 6006; MITOCHONDRIAL ENZYME; NITIDINE; PROTOBERBERINE DERIVATIVE; SAINTOPIN; TOPOTECAN; UCE 1022; UCE 6; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTINEOPLASTIC ACTIVITY; DNA CLEAVAGE; DRUG CYTOTOXICITY; DRUG MECHANISM; DRUG RESISTANCE; ENZYME STRUCTURE; GENE MUTATION; REVIEW; STRUCTURE ACTIVITY RELATION;

EID: 0032033603     PISSN: 03009084     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0300-9084(98)80008-4     Document Type: Article

References (200)

1. 1 Wang JC (1996) DNA topoisomerases. Annu Rev Biochem 65, 635-692
2. 2 Gupta M, Fujimori A, Pommier Y (1995) Eukaryotic DNA topoisomerases 1. Biochim Biophys Acta 1262, 1-14
3. 3 Wang JC (1985) DNA topoisomerases. Annu Rev Biochem 54, 665-697
4. 4 Froelich-Ammon SJ, Osheroff N (1995) Topoisomerase Poisons: Harnessing the dark side of enzyme mechanism. J Biol Chem 270, 21429-21432
5. 5 Wang JC (1987) Recent studies of DNA topoisomerases. Biochim Biophys Acta 909, 1-9
6. 6 Gellert M (1981) DNA topoisomerases. Annu Rev Biochem 50, 879-910
7. 7 Liu LF (1989) DNA topoisomerase poisons as antitumor drugs. Annu Rev Biochem 58, 351-375
8. 8 Pommier Y, Tanizawa A (1993) Mammalian DNA topoisomerase I and its inhibitors. In: Cancer Chemotherapy (Hickman J, Tritton T, eds) Blackwell Scientific Publications, Oxford, 214-250
9. 9 Wallis JW, Chrebet G, Brodsky G, Rolfe M, Rothstein R (1989) A hyper-recombination mutation in S cerevisiae identifies a novel eukaryotic topoisomerase. Cell 58, 409-419
10. 10 Hanai R, Caron PR, Wang JC (1996) Human TOP3: a single copy gene encoding DNA topoisomerase III. Proc Natl Acad Sci USA 93, 3653-3657
11. 11 Kim RA, Wang JC (1992) Identification of the yeast TOP3 gene product as a single strand-specific DNA topoisomerase. J Biol Chem 267, 17178-17185
12. 12 Fritz E, Elsea SH, Patel PI, Meyn MS (1997) Overexpression of a truncated human topoisomerase III partially corrects multiple aspects of the ataxia-telangiectesia phenotype. Proc Natl Acad Sci USA 94, 4538-4542
13. 13 Gangloff S, MacDonald JP, Bendixen C, Arthur L, Rothstein R (1994) The yeast type 1 topoisomerase top3 interacts with sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase. Mol Cell Biol 14, 8391-8398
14. 14 Wallis JW, Chrebet G, Brodsky G, Rolfe M, Rothstein R (1989) A hypersensitive recombination mutation in S cerevisiae identifies a novel eukaryotic topoisomerase. Cell 58, 409-419
15. 15 Pulleyblank DE, Morgan AR (1975) Partial purification of protein from calf thymus. Biochemistry 14, 5206-5209
16. 16 Hsieh T, Brutlag D (1980) ATP-dependent DNA topoisonmerase from D. melanogaster reversibly catenates duplex DNA rings. Cell 21, 115-125
17. 17 Liu LF (1983) HeLa toposiomerase I. Methods Enzymol 100, 133-137
18. 18 Koiwai O, Yasui Y, Sakai Y, Watanabe T, Ishii K, Yanagihara S, Andoh T (1993) Cloning of mouse cDNA encoding DNA topoisomerase I and chromosomal location of the gene. Gene 125, 211-216
19. 19 Tanizawa A, Tabuchi A, Bertrand R, Pommier Y (1993) Cloning of Chinese hamster DNA topoisomerase I cDNA and identification of a single point mutation responsible for camptothecin resistance. J Biol Chem 268, 25463-25468
20. 20 Brun G, Vannier P, Scovassi I, Callen J-C (1981) DNA topoisomerase I from mitochondria of Xenopus laevis oocytes. Eur J Biochem 118, 407-415
21. 21 Castora FJ and Kelly WG (1986) ATP inhibits nuclear and mitochondrial type I topoisomerases from human leukemia cells. Proc Natl Acad Sci USA 83, 1680-1684
22. 22 Lazarus GM, Henrich JP, Kelly WG, Schmitz SA, Castora FJ (1987) Purification and characterization of a type I DNA topoisomerase from calf thymus mitochondria. Biochemistry 26, 6195-6203
23. 23 Lee MP, Brown SD, Chen A, Hsieh T-S (1993) DNA topoisomerase I is essential in Drosophila melanogaster. Proc Natl Acad Sci USA 90, 6656-6660
24. 24 Morham S, Kluckman KD, Voulomanos N, Smithies O (1996) Targeted disruption of the mouse topoisomerase I gene by camptothecin selection. Mol Cell Biol 16, 6804-6809
25. 25 Fernandez-Beros M-E and Tse-Dinh Y-C (1992) Conditional growth of Escherichia coli caused by expression of vaccinia virus DNA topoisomerase I. J Bacteriol 174, 7059-7062
26. 26 Bjornsti M-A, Benedetti P, Viglianti GA, Wang JC (1989) Expression of human DNA topoisomerase I in Yeast cells lacking yeast DNA topoisomerase I: restoration of sensitivity of the cells to the antitumor drug camptothecin. Cancer Res 49, 6318-6323
27. 27 Madden KR, Champoux JJ (1992) Overexpression of human topoisomerase I in baby hamster kidney cells: hypersensitivity of clonal isolates to camptothecin. Cancer Res 52, 525-532
28. 28 Heck MM, Hittelman WN, Earnshaw WC (1988) Differential expression of DNA topoisomerases I and II during the eukaryotic cell cycle. Proc Natl Acad Sci USA 85, 1086-1090
29. 29 Romig H and Richter A (1990) Expression of the topoisomerase I gene in serum stimulated human fibroblasts. Biochim Biophys Acta 1048, 274-280
30. 30 Thrash C, Voelkel K, DiNardo S, Sternglanz R (1984) Identification of Saccharomyces cerevisiae mutants deficient in DNA topoisomerase I activity. J Biol Chem 259, 1375-1377
31. 31 Uemura T, Yanagida M (1984) Isolation of type I and II DNA topoisomerase mutants from fission yeast: Single and double mutants show different phenotypes in cell growth and chromatin organization. EMBO J 3, 1337-1351
32. 32 Christman MF, Dietrich FS, Fink GR (1988) Mitotic recombination in the rDNA of S cerevisiae is suppressed by the combined action of DNA topoisomerase I and II. Cell 55, 413-425
33. 33 Kim RA and Wang JC (1989) A subthreshold level of DNA topoisomerase leads to the excision of yeast rDNA as extrachromosomal rings. Cell 57, 975-985
34. 34 Nitiss JL, Rose A, Sykes KC, Harris J, Zhou J (1996) Using yeast to understand drugs that target topoisomerases. Ann NY Acad Sci 803, 32-43
35. 35 Goldman GH, Yu C, Wu H-Y, Sanders MM, La Voie EJ, Liu LF (1997) Differential poisoning of human and Aspergillus nidulans DNA topoisomerase I by bi- and terbenzimidazoles. Biochemistry 36, 6488-6494
36. 36 Knab AM, Fertala J, Bjornsti M-A (1993) Mechanisms of camptothecin resistance in Yeast DNA topoisomerase I mutants. J Biol Chem 268, 22322-22330
37. 37 Bauer WR, Ressner EC, Kates J, Patzke JV (1977) A DNA nicking-closing enzyme encapsidated in vaccinia virus: partial purification and properties. Proc Natl Acad Sci USA 74, 1841-1845
38. 38 Shaffter R, Traktman P (1987) Vaccinia virus encapsidates a novel topoisomerase with the proteries of eukaryotic type I enzyme. J Biol Chem 262, 9309-9315
39. 39 Shuman S, Moss B (1987) Identification of a vaccinia virus gene encoding a type I DNA topoisomerase. Proc Natl Acad Sci USA 84, 7478-7482
40. 40 Upton C, Opgenorth A, Traktman P, McFadden G (1990) Identification and DNA sequence of the Shope fibroma virus DNA topoisomerase I gene. Virology 176, 439-447
41. 41 Zantinge JL, Krell PJ, Derbyshire JB, Nagy E (1996) Partial transcriptional mapping of the fowlpox virus genome and analysis of the EcoRI L fragment. J Gen Virol 77, 603-614
42. 42 Shchelkunov SN, Blinov VM, Sandakhchiev LS (1993) Genes of variola and vaccinia viruses necessary to overcome the host protective mechanisms. FEBS Lett 319, 80-83
43. 43 Traktman P (1996) Poxvirus DNA replication. In: DNA replication in eukaryotic cells (DePamphilis ML, ed) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 775-798
44. 44 Shuman S (1991) Site-specific DNA cleavage by Vaccinia virus DNA topoisomerase I. Role of nucleotide sequence and DNA secondary structure. J Biol Chem 266, 1796-1803
45. 45 Palaniyar N, Fisher C, Parks R, Evans DH (1996) SFV topoisomerase: sequence specificity in a genetically mapped interval. Virology 221, 351-354
46. 46 Priel E, Showalter SD, Roberts M, Oroszlan S, Segal S, Aboud M, Blair DG (1990) Topoisomerase I activity associated with human immunodeficiency virus (HIV) particles and equine infectious anemia virus core. EMBO J 9, 4167-4172
47. 47 Li CJ, Zhang LJ, Dezube BJ, Crumpacker CS, Pardee AB (1993) Three inhibitors of type 1 human immunodeficiency virus long terminal repeat-directed gene expression and virus replication. Proc Natl Acad Sci USA 90, 1839-1842
48. 48 Zhang JL, Sharma PL, Li CJ, Dezube BJ, Pardee AB, Crumpacker CS (1997) Topotecan inhibits human immunodeficiency virus type I infection through a topoisomerase I-independent mechanism in a cell line with altered topoisomerase I. Antimicrob Agents Chemother 41, 977-981
49. 49 Takahashi H, Matsuda M, Kojima A, Sata T, Andoh T, Kurata T, Nagashima K, Hall WW (1995) Human immunodeficiency virus type 1 reverse transcriptase: enhancement of activity by interaction with cellular topoisomerase I. Proc Natl Acad Sci USA 92, 5694-5698
50. 50 Jardine D, TAchedjian G, Locarnini S, Birch C (1994) Cellular topoisomerase I associated with HIV-1. AIDS Res Hum Retroviruses 9, 1245-1250
51. 51 Schaak J, Schedl P, Shenk T (1990) Topoisomerase I and II cleavage of adenovirus DNA in vivo: both topoisomerase activities appear to be required for adenovirus replication. J Virol 64, 78-85
52. 52 Kawanishi M (1993) Topoisomerase I and II activities are required for Epstein-Barr virus replication. J Gen Virol 74, 2263-2268
53. 53 Yamada Y, Yamamoto N, Maeno K, Nishiyama Y (1990) Role of DNA topoisomerase I in the replication of herpes simplex virus type 2. Arch Virol 110, 121-127
54. 54 Stewart L, Ireton GC, Champoux JJ (1997) Reconstitution of human topoisomerase I by fragment complementation. J Mol Biol 269, 355-372
55. 55 Stewart L, Ireton G, Champoux JJ (1996) The domain organization of human topoisomerase I. J Biol Chem 271, 7602-7608
56. 56 Stewart L, Ireton G, Parker L, Madden KR, Champoux JJ (1996) Biochemical and Biophysical analyses of recombinant forms of human topoisomerase I. J Biol Chem 271, 7593-7601
57. 57 Liu LF, Miller KG (1981) Eukaryotic DNA topoisomerases: two forms of type IDNA topoisomerases from HeLa cell nuclei. Proc Natl Acad Sci USA 78, 3487-3491
58. 58 D'Arpa P, Machlin PS, Ratrie H, 3d., Rothfield NF, Cleveland DW, Earnshaw WC (1988) cDNA cloning of human DNA topoisomerase I: catalytic activity of a 67.7-kDa carboxyl-terminal fragment. Proc Natl Acad Sci USA 85, 2543-2547
59. 59 Pommier Y, Kerrigan D, Hartmann KD, Glazer RI (1990) Phosphorylation of mammalian DNA topoisomerase I and activation by protein C. J Biol Chem 265, 9418-9422
60. 60 Kikuchi A and Miyaike M (1993) Expression of human type I and II DNA topoisomerases and their derivatives in Escherichia coli. In: Molecular biology of DNA topoisomerases and its application to chemotherapy (Andoh T, Ikeda H, Oguro M, eds) CRC Press, Boca Raton, 121-130
61. 61 Madden KR, Stewart L, Champoux JJ (1995) Preferential binding of human topoisomerase I to superhelical DNA. EMBO J 14, 5399-5409
62. 62 Nitiss J, Wang JC (1988) DNA topoisomerase-targeting antitumor drugs can be studied in yeast. Proc Natl Acad Sci USA 85, 7501-7505
63. 63 Pommier Y, Gupta M, Valenti M, Nieves-Neira W (1996) Cellular resistance to camptothecins. In: The camptothecins: from discovery to the patient (Pantazis P, Giovanella BC, Rothenberg ML, eds) The New York Academy of Sciences, New York, 60-73
64. 64 Pommier Y (1996) Eukaryotic DNA topoisomerase I: genome gate keeper and its intruders, camptothecins. Sem Oncol 23, 1-10
65. 65 Pommier Y, Leteurtre F, Fesen M, Fujimori A, Bertrand R, Solary E, Kohlhagen G, Kohn KW (1994) Cellular determinants of sensitivity and resistance to DNA topoisomerase inhibitors. Cancer Invest 12, 530-542
66. 66 Wall ME, Wani MC, Cooke CE, Palmer KH, McPhail AT, Slim GA (1966) The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata. J Am Chem Soc 88, 3888-3890
67. 67 Giovanella BC, Stehlin JS, Wall ME, Wani MC, Nicholas AW, Liu LF, Silber R, Potmesil M (1989) DNA topoisomerase I-targeted chemotherapy of human colon cancer in xenografts. Science 246, 1046-1048
68. 68 Slichenmyer WJ, Rowinsky EK, Donehower RC, Kaufmann SH (1993) The current status of camptothecin analogs as anticancer agents. J Natl Cancer Inst 85, 271-287
69. 69 Armand JP, Ducreux M, Mahjoubi M, Abigerges D, Bugat R, Chabot G, Herait P, de Forni M, Rougier P (1995) CPT-11 (irinotecan) in the treatment of colorectal cancer. Eur J Cancer 31A, 1283-1287
70. 70 O'Reilly S, Rowinsky EK (1996) The clinical status of irinotecan (CPT-11), a novel water soluble camptothecin analogue: 1996. Crit Rev Oncol/Hematol 24, 47-70
71. 71 Dancey J and Eisenhauer EA (1996) Current perspectives on camptothecins in cancer treatment [editorial]. Br J Cancer 74, 327-338
72. 72 Tanizawa A, Fujimori A, Fujimori Y, Pommier Y (1994) Comparison of topoisomerase I inhibition, DNA damage, cytotoxicity of camptothecin derivatives presently in clinical trials. J Natl Cancer Inst 86, 836-842
73. 73 Tanizawa A, Kohn KW, Kohlhagen G, Leteurtre F, Pommier Y (1995) Differential stabilization of eukaryotic DNA topoisomerase I cleavage complexes by camptothecin derivatives. Biochemistry 43, 7200-7206
74. 74 Covey JM, Jaxel C, Kohn KW, Pommier Y (1989) Protein-linked DNA strand breaks induced in Mammalian cells by camptothecin, an inhibitor of topoisomerase I. Cancer Res 49, 5016-5022
75. 75 Hsiang YH, Hertzberg R, Hecht S, Liu LF (1985) Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem 260, 14873-14878
76. 76 Jaxel C, Capranico G, Kerrigan D, Kohn KW, Pommier Y (1991) Effect of local DNA sequence on topoisomerase I cleavage in the presence or absence of camptothecin. J Biol Chem 266, 20418-20423
77. 77 Porter SE and Champoux JJ (1989) Mapping in vivo topoisomerase I sites on simian virus 40 DNA: asymmetric distribution of sites on replicating molecules. Mol Cell Biol 9, 541-550
78. 78 Bonven BJ, Gocke E, Westergaard O (1985) A high affinity topoisomerase I binding sequence is clustered at DNAase I hypersensitive sites in Tetrahymena R-chromatin. Cell 41, 541-551
79. 79 Zhang H, Wang JC, Liu LF (1988) Involvement of DNA topoisomerase I in transcription of human ribosomal RNA genes. Proc Natl Acad Sci USA 85, 1060-1064
80. 80 Stewart AF, Herrera RE, Nordheim A (1990) Rapid induction of c-fos transcription reveals quantitive linkage of RNA polymerase II and DNA topoisomerase I enzyme activities. Cell 60, 141-146
81. 81 Gilmour DS and Elgin SC (1987) Localization of specific topoisomerase I interactions within the transcribed region of active heat shock genes by using the inhibitor camptothecin. Mol Cell Biol 7, 141-148
82. 82 Kroeger PE and Rowe TC (1989) Interaction of topoisomerase I with the transcribed region of the Drosophila HSP 70 heat shock gene. Nucleic Acids Res 17, 8495-8509
83. 83 Stewart AF, Schütz G (1987) Camptothecin-induced in vivo topoisomerase I cleavages in the transcriptionally active tyrosine amino-transferase gene. Cell 50, 1109-1117
84. 84 Bronstein IB, Gromova II, Razin SV (1991) Specific cleavage of chicken alpha-A-globin and human c-Ha-ras genes by two molecular forms of calf thymus topoisomerase I. Mol Cell Biochem 101, 115-124
85. 85 Perez-Stable C, Shen CC, Shen C-KJ (1988) Enrichement and depletion of Hela topoisomerase I recognition sites among specific types of DNA elements. Nucleic Acids Res 16, 7975-7993
86. 86 Thomsen B, Mollerup S, Bonven BJ, Frank R, Blöcker H, Nielsen OF, Westergaard O (1987) Sequence specificity of DNA topoisomerase I in the presence and absence of camptothecin. EMBO J 6, 1817-1823
87. 87 Porter SE, Champoux JJ (1989) The basis for camptothecin enhancement of DNA breakage by eukaryotic topoisomerase I. Nucleic Acids Res 17, 8521-8532
88. 88 Tanizawa A, Kohn KW, Pommier Y (1993) Induction of cleavage in topoisomerase I cDNA by topoisomerase I enzymes from calf thymus and wheat germ in the presence and absence of camptothecin. Nucleic Acids Res 21, 5157-5166
89. 89 Jaxel C, Kohn KW, Pommier Y (1988) Topoisomerase I interaction with SV40 DNA in the presence and absence of camptothecin. Nucleic Acids Res 16, 11157-11170
90. 90 Tanizawa A, Kohn K, Pommier Y (1993) Induction of cleavage in topoisomerase I c-DNA by topoisomerase I enzymes from calf thymus and wheat germ in the presence and absence of camptothecin. Nucleic Acids Res 21, 5157-5166
91. 91 Pommier Y, Kohlhagen G, Kohn F, Leteurtre F, Wani MC, Wall ME (1995) Interaction of an alkylating camptothecin derivative with a DNA base at topoisomerase I-DNA cleavage sites. Proc Natl Acad Sci USA 92, 8861-8865
92. 92 Pommier Y, Fujimori A, Hoki Y, Gupta M, Gariboldi M (1996) DNA topoisomerase I inhibitors and multidrug resistance. In: Multidrug resistance in cancer cells (Gupta S, Tsuruo T, eds) John Willey, Oxford, 119-135
93. 93 Fujimori A, Harker WG, Kohlhagen G, Hoki Y, Pommier Y (1995) Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell resistant to camptothecin. Cancer Res 55, 1339-1346
94. 94 Fujimori A, Harker WG, Kohlhagen G, Hoki Y, Pommier Y (1994) Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecin. Cancer Res, in press
95. 95 Ohashi N, Fujiwara Y, Yamaoka N, Katoh O, Satow Y, Yamakido M (1996) No alteration in DNA topoisomerase I gene related to CPT-11 resistance in human lung cancer. Jpn J Cancer Res 87, 1280-1287
96. 96 Takatani H, Oka M, Fukuda M, Narasaki F, Nakano R, Ikeda K, Terashi K, Kinshita A, Soda H, Kanda T, Schneider E, Kohno S (1997) Gene mutation analysis and quantitation of DNA topoisomerase I in previously untreated non-small cell lung carcinomas. Jpn J Cancer Res 88, 160-165
97. 97 Yang C-HJ, Horton JK, Cowan KH, Schneider E (1995) Cross-resistance to camptothecin analogues in mitoxantrone-resistant human breast carcinoma cell line is not due to DNA topoisomerase I alterations. Cancer Res 55, 4004-4009
98. 98 Beidler DR, Chang J-Y, Zhou B-S, Cheng Y-C (1995) Camptothecin resistance involving steps subsequent to the formation of protein-linked DNA breaks in human camptothecin-resistant KB cell lines. Cancer Res 56, 345
99. 99 Fujimori A, Gupta M, Hoki Y, Pommier Y (1996) Acquired resistance of human breast cancer MCF-7/C4 cells with normal topoisomerase I and elevated DNA repair. Mol Pharmacol 50, 1472-1478
100. 100 Kauh EA and Bjornsti M-A (1995) SCT1 mutants suppress the camptothecin sensitivity of yeast cells expressing wild-type DNA topoisomerase I. Proc Natl Acad Sci USA 92, 6299-6303
101. 101 Fujimori A, Hoki Y, Popescu N, Pommier Y (1996) Silencing and selective methylation of the normal topoisomerase I gene in camptothecin-resistant CEM/C2 human leukemia cells. Oncol Res 295-301
102. 102 Harker WG, Slade KL, Parr RL, Feldhoff PW, Sullivan DM, Holguin MH (1995) Alterations in the topoisomerase IIα gene, messenger RNA, subcellular protein distribution as well as reduced expression of the DNA topoisomerase IIβ enzyme in a mitoxantrone-resistant HL-60 human leukemia cell line. Cancer Res 55, 1707-1716
103. 103 Leteurtre F, Fesen M, Kohlhagen G, Kohn KW, Pommier Y (1993) Specific interaction of camptothecin, a topoisomerase I inhibitor, with guanine residues of DNA detected by photoactivation at 365 nm. Biochemistry; 32, 8955-8962
104. 104 Jaxel C, Kohn KW, Wani MC, Wall ME, Pommier Y (1989) Structure-activity study of the actions of camptothecin derivatives on mammalian topoisomerase I: evidence for a specific receptor site and a relation to antitumor activity. Cancer Res 49, 1465-1469
105. 105 Pommier Y, Jaxel C, Heise C, Kerrigan D, Kohn KW (1991) Structure-Activity Relationship of Topoisomerase I Inhibition by Camptothecin Derivatives: Evidence for the Existence of a Ternary Complex. In: DNA topoisomerases in cancer (Potmesil M, Kohn KW, eds) Oxford University Press, New York, 121-132
106. 106 Wall ME and Wani MC (1995) Camptothecin and taxol: discovery to clinic - thirteenth Bruce F. Cain Memorial Award lecture. Cancer Res 55, 753-760
107. 107 Hsiang Y-H, Liu LF, Wall ME, Wani MC, Nicholas AW, Manikumar G, Kirschenbaum S, Silber R, Potmesil M (1989) DNA topoisomerase I-mediated DNA cleavage and cytotoxicity of camptothecin analogs. Cancer Res 49, 4385-4389
108. 108 Luzzio MJ, Besterman JM, Emerson DL, Evans MG, Lackey K, Leitner PL, McIntyre G, Morton B, Myers PL, Peel M, Sisco JM, Sternbach DD, Tong W-Q, Truesdale A, Uehling DE, Vuong A, Yates J (1995) Synthesis and antitumor activity of novel water-soluble derivatives of camptothecin as specific inhibitors of topoisomerase I. J Med Chem 38, 395-401
109. 109 Taagepera S, Rao PN, Drake FH, Gorbsky GJ (1993) DNA topoisomerase II-alpha is the major chromosome protein recognized by the mitotic phosphoprotein antibody MPM-2. Proc Natl Acad Sci USA 90, 8407-8411
110. 110 Pommier Y, Tanizawa A, Kohn KW (1994) Mechanisms of topoisomerase I inhibition by anticancer drugs. Adv Pharmacol 29B, 73-91
111. 111 Crow RT and Crothers DM (1994) Inhibition of topoisomerase I by anthracycline antibiotics: evidence for general inhibition of topoisomerase I by DNA-binding agents. J Med Chem 37, 3191-3194
112. 112 Hirabayashi N, Kim R, Nishiyama M, Aogi K, Saeki S, Toge T, Okada K (1992) Tissue expression of topoisomerase I and II in digestive tract cancers and adjacent normal tissues. Proc Am Assoc Cancer Res 33, 436
113. 113 van der Zee AGJ, Hollema H, de Jong S, Boonstra H, Gouw A, Willemse PHB, Zijlstra JG, de Vrie EGE (1991) P-glycoprotein expression and DNA topoisomerase I and II activity in benign tumors of the ovary and in malignant tumors of the ovary, before and after platinum/cyclophosphamide chemotherapy. Cancer Res 51, 5915-5920
114. 114 Potmesil M, Giovanella BC, Wall ME, Liu LF, Silber R, Stehlin JS, Wani MC, Hoechster H (1993) Preclinical and clinical development of DNA topoisomerase I inhibitors in the United States. In: Molecular Biology of DNA topoisomerases and its application to chemotherapy (Andoh T, Ikeda H, Oguro M, eds) CRC Press, Boca Raton, FL, 301-311
115. 115 Goldwasser F, Bae IS, Torres K, Pommier Y (1995) Topoisomerase I-related parameters and camptothecin activity in the colon cell lines from the National Cancer Institute anticancer screen. Cancer Res 55, 2116-2121
116. 116 Perego P, Capranico G, Supino R, Zunino F (1994) Topoisomerase I gene expression and cell sensitivity to camptothecin in human cell lines of different tumor types. Anti-Cancer Drugs 5, 645-649
117. 117 Pommier Y, Bertrand R, Solary E (1994) Apoptosis induced by DNA topoisomerase I and II inhibitors in human leukemia HL-60 cells. Leuk Lymphoma 15, 21-32
118. 118 Hsiang Y-H, Lihou MG, Liu LF (1989) Arrest of DNA replication by drug-stabilized topoisomerase I-DNA cleavage complexes as a mechanism of cell killing by camptothecin. Cancer Res 49, 5077-5082
119. 119 Holm C, Covey JM, Kerrigan D, Pommier Y (1989) Differential requirement of DNA replication for the cytotoxicity of DNA topoisomerase I and II inhibitors in Chinese hamster DC3F cells. Cancer Res 49, 6365-6368
120. 120 Bertrand R, Kerrigan D, Sarang M, Pommier Y (1991) Cell death induced by topoisomerase inhibitors: role of calcium in mammalian cells. Biochem Pharmacol 42, 77-85
121. 121 Ryan AJ, Squires S, Strutt HL, Johnson RT (1991) Camptothecin cytotoxicity in mammalian cells is associated with the induction of persistent double strand breaks in replicating DNA. Nucleic Acids Res 19, 3295-3300
122. 122 Shin C-G and Snapka RM (1990) Exposure to camptothecin breaks leading and lagging strand simian virus 40 DNA replication forks. Biochem Biophys Res Commun 168, 135-140
123. 123 Yang L, Wold MS, Li JJ, Kelly TJ, Liu LF (1987) Roles of DNA topoisomerases in simian virus 40 DNA replication in vitro. Proc Natl Acad Sci USA 84, 950-954
124. 124 Henningfeld KA and Hecht S (1995) A model for topoisomerase I-mediated insertions and deletions with duplex DNA substrates containing branches, nicks, gaps. Biochemistry 34, 6120-6129
125. 125 Bullock P, Champoux JJ, Botchan M (1985) Association of crossover points with topoisomerase I cleavage sites: a model for nonhomologous recombination. Science 230, 954-958
126. 126 Pommier Y, Jenkins J, Kohlhagen G, Leteurtre F (1995) DNA recombinase activity of eukaryotic DNA topoisomerase I; Effects of camptothecin and other inhibitors. Mutat Res 337, 135-145
127. 127 Anderson RD, Berger NA (1994) Mutagenicity and carcinogenicity of topoisomerase-interactive drugs. Mutat Res 309, 109-142
128. 128 Chatterjee S, Cheng M-F, Trivedi D, Petzold SJ, Berger NA (1989) Camptothecin hypersensitivity in poly (adenosine diphosphate-ribose) polymerase-deficient cell lines. Cancer Commun 1, 389-394
129. 129 Ratain MJ and Rowley JD (1992) Therapy-related acute myeloid leukemia secondary to inhibitors of topoisomerase II: From the bed-side to the target genes. Ann Oncol 3, 107-111
130. 130 Nichols CR, Breeden ES, Loehrer PJ, Williams SD, Einhorn LH (1993) Secondary leukemia associated with a conventional dose of etoposide: review of a serial germ cell tumor protocols. J Natl Cancer Inst 85, 36-40
131. 131 Ross JA, Potter JD, Robison LL (1994) Infant leukemia, topoisomerase II inhibitors, the MLL gene. J Natl Cancer Inst 86, 1678-1680
132. 132 Zeleznik-Le NJ, Harden AM, Rowley JD (1994) 11q23 traslocations split the 'AT-hook' cruciform DNA-binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene. Proc Natl Acad Sci USA 91, 10610-10614
133. 133 Bendixen C, Thomsen B, Alsner J, Westergaard O (1990) Camptothecin-stabilized topoisomerase I-DNA adducts cause premature termination of transcription. Biochemistry 29, 5613-5619
134. 134 Holm C, Stearns T, Botstein D (1989) DNA topoisomerase II must act at mitosis to prevent nondisjunction and chromosome breakage. Mol Cell Biol 9, 159-168
135. 135 Goldwasser F, Shimizu T, Jackman J, Hoki Y, O'Connor PM, Kohn KW, Pommier Y (1996) Correlations between S- and G2-phase arrest and cytotoxicity of camptothecin in human colon carcinoma cells. Cancer Res 56, 4430-4437
136. 136 Valenti M, Nieves-Neira W, Kohlhagen G, Kohn KW, Wall ME, Wani MC, Pommier Y (1997) Novel 7-alkyl methylenedioxycamptothecin derivatives exhibit increased cytotoxicity and induce persistent cleavage complexes both with purified mammalian topoisomerase I and in human colon carcinoma SW620 cells. Mol Pharmacol 52, 82-87
137. 137 Pommier Y, Fesen MR, Goldwasser F (1996) Topoisomerase II inhibitors: the epipodophyllotoxins, m-AMSA, the ellipticine derivatives. In: Cancer chemotherapy and biotherapy: principles and practice (Chabner BA, Longo DL, eds) 2nd edn, Lippincott-Raven, Philadelphia, 435-461
138. 138 Yamashita Y, Kawada S-Z, Fujii N, Nakano H (1991) Induction of mammalian topoisomerase I and II mediated DNA cleavage by saintopin, a new antitumor agent from fungus. Biochemistry 30, 5838-5845
139. 139 Fujii N, Yamashita Y, Chiba S, Uosaki Y, Saitoh Y, Tuji Y, Nakano H (1993) UCE6, a new antitumor antibiotic with topoisomerase I mediated DNA cleavage activity, from actinomycetes [letter]. J Antibiot 46, 1173-1174
140. 140 Fujii N, Yamashita Y, Ando K, Agatsuma T, Saitoh Y, Gomi K, Nishiie Y, Nakano H (1994) UCE1022, a new antitumor antibiotic with topoisomerse I mediated DNA cleavage activity from Paecilomyces. J Antibiot (Tokyo) 47, 949-951
141. 141 Fujii N, Yamashita Y, Mizukami T, Nakano H (1997) Correlation between the formation of cleavage complex with topoisomerase I and growth-inhibitory activity of saintopin-type antibiotics. Mol Pharmacol 51, 269-276
142. 142 Leteurtre F, Fujimori A, Tanizawa A, Chhabra A, Mazumder A, Kohlhagen G, Nakano H, Pommier Y (1994) Saintopin, a dual inhibitor of DNA topoisomerases I and II, as a probe for drug-enzyme interactions. J Biol Chem 269, 28702-28707
143. 143 Fang S-D, Wang L-K, Hecht SM (1993) Inhibitors of DNA topoisomerase I isolated from the roots of Zanthoxylum nitidum. J Org Chem 58, 5025-5027
144. 144 Wang L-K, Johnson RK, Hecht SM (1993) Inhibition of topoisomerase I function by nitidine and fagaronine. Chem Res Toxicol 6, 813-818
145. 145 Larsen AK, Grondard L, Couprie J, Desoizé B, Comof L, Jardillier J-C, Riou J-F (1993) The antileukemic alkaloid fagaronine is an inhibitor of DNA topoisomerases I and II. Biochem Pharmacol 19, 1403-1412
146. 146 Janin YL, Croisy A, Riou J-F, Bisagni E (1993) Synthesis and evaluation of new 6-amino-substituted benzo[c]phenanthridine derivatives. J Med Chem 36, 3686-3692
147. 147 Suffness M and Cordell GA (1985) Antitumor alkaloids. In: The alkaloids (Brossi A, ed) Vol XXV, Academic Press, Orlando, 178-188
148. 148 Zee-Cheng K, Paull K, Cheng C (1974) Experimental antileukemic agents: coralyne, analogs, related compounds. J Med Chem 17, 347-351
149. 149 Gatto B, Sanders MM, Yu C, Wu HY, Makhey D, LaVoie EJ, Liu LF (1996) Identification of topoisomerase I as the cytotoxic target of the protoberberine alkaloid coralyne. Cancer Res 56, 2795-2800
150. 150 Wang LK, Rogers BD, Hecht SM (1996) Inhibition of topoisomerase I function by coralyne and 5, 6-dihydrocoralyne. Chem Res Toxicol 9, 75-83
151. 151 Kobayashi Y, Yamashita Y, Fujii N, Takaboshi K, Kawakami T, Kawamura M, Mizukami T, Nakano H (1995) Inhibitors of DNA topoisomerase I and II isolated from the Coptis rhizomes. Planta Med 61, 414-418
152. 152 Poddevin B. Riou J-F, Lavelle F, Pommier Y (1993) Dual topoisomerase I and II inhibition by intoplicine (RP-60475) a new antitumor agent in early clinical trials. Mol Pharmacol 44, 767-774
153. 153 Nabiev I, Chourpa I, Riou J-F, Nguyen CH, Lavelle F, Manfait M (1994) Molecular interactions of DNA-topoisomerase I and II inhibitor with DNA and topoisomerases and in ternary complexes: binding modes and biological effects for intoplicine derivatives. Biochemistry 33, 9013-9023
154. 154 Abigerges D, Armand JP, Chabot GG, Bruno R, Bissery MC, Bayssas M, Klink-Alakl M, Clavel M, Catimel G (1996) Phase I and pharmacology study of intoplicine (RP 60475; NSC 645008), novel topoisomerase I and II inhibitor, in cancer patients. Anticancer Drugs 7, 166-174
155. 155 Riou J-F, Helissey P, Grondard L, Giorgi-Renault S (1991) Inhibition of eukaryotic DNA topoisomerase I and II activities by indoloquinolinedione derivatives. Mol Pharmacol 40, 699-706
156. 156 Callais F, Helissey P, Min S, Festy B, Giorgi-Renault S (1994) Structure-mutagenicity relationships in series of 11H-indolo[3, 2-c]quinoline-1, 4-diones, tetrahydro-11H-indolo[3, 2-c]quinoline-1, 4-diones and 11H-pyrido[3′, 4′:4, 5]pyrrolo[3, 2-c]quinoline-1, 4-diones with leukemia cytotoxic properties. Relations with topoisomerase I inhibiting properties. Mutat Res 311, 149-156
157. 157 Kokoshka JM, Capson TL, Holden JA, Ireland CM, Barrows LR (1996) Differences in the topoisomerase I cleavage complexes formed by camptothecin and wakayin, a DNA-intercalating marine natural product. Anticancer Drugs 7, 758-765
158. 158 Paull KD, Shoemaker RH, Hodes L, Monks A, Scudiero DA, Rubinstein L, Plowman J, Boyd M (1989) Display and analysis of patterns of differential activity of drugs against human tumor cell lines: development of a mean graph and COMPARE algorithm. J Natl Cancer Inst 81, 1088-1092
159. 159 Boyd MR and Paull KD (1995) Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery screen. Drug Dev Res 34, 91-109
160. 160 Kohlhagen G, Paull KD, Pommier Y (1996) NSC 314622 a new poison of eukaryotic topoisomerase I. Proc Am Assoc Cancer Res 37, 431
161. 161 Kohlhagen G, Paull KT, Cushman M, Pommier Y (1997) NSC314622, a novel topoisomerase I poison with unique chemical structure. Mol Pharmacol, in press
162. 162 Kawada S-Z, Yamashita Y, Uosaki Y, Gomi K, Iwasaki T, Takiguchi T, Nakano H (1992) UCT48, a new antitumor antibiotic with topoisomerase II mediated DNA cleavage activity from Streptomyces sp. J Antibiot 45, 1182-1184
163. 163 Yamashita Y, Fujii N, Murakata C, Ashizawa T, Okabe M, Nakano H (1992) Induction of mammalian DNA topoisomerase I-mediated DNA cleavage by antitumor indolocarbazole derivatives. Biochemistry 31, 12069-12075
164. 164 Yoshinari T, Yamada A, Uemura D, Nomura K, Arakawa H, Kojiri K, Yoshida E, Suda H, Okura A (1993) Induction of topoisomerase I-mediated DNA cleavage by a new indolocarbazole, ED-110. Cancer Res 53, 490-494
165. 165 Yoshinari T, Matsumoto M, Arakawa H, Okada H, Noguchi K, Suda H, Okura A, Nishimura S (1995) Novel antitumor indolocarbazole compound 6-N-formylamino-12, 13-dihydro-1, 11-dihydroxy-13-(β-D-glucopyranosyl)-5H-indolo[2, 3-a] pyrrolo[3, 4-c] carbazole-5, 7 (6H)-dione (NB-506): induction of Topoisomerase I-mediated DNA cleavage and mechanisms of cell line-selective cytotoxicity. Cancer Res 55, 1310-1315
166. 166 Kanzawa F, Nishio K, Kubuta N, Saijo N (1995) Antitumor activities of a new indolocarbazole substance, NB-506, establishment of NB-506-resistant cell lines, SBC-3/NB. Cancer Res 55, 2806-2813
167. 167 Bertrand R, Solary E, Kohn KW, O'Connor P, Pommier Y (1994) Induction of a common pathway to apoptosis by staurosporine. Exp Cell Res 211, 314-321
168. 168 Shao R-G, Shimizu T, Pommier Y (1997) 7-hydroxystaurosporine (UCN-01) induces apoptosis in human colon carcinoma and leukemia cells independently of p53. Exp Cell Res 234, 388-397.
169. 169 Arakawa H, Iguchi T, Morita M, Yoshinari T, Kojiri K, Suda H, Okura A, Nishimura S (1995) Novel indolocarbazole compound 6-N4-formylamino-12, 13-dihydro-1, 11-dihydroxy-13-(β-D-glucopyranosyl)-5H-indolo[2, 3-a]pyrrolo-[3, 4-c]carbazole-5, 7-(6H)-dione (NB-506): its potent antitumor activities in mice. Cancer Res 55, 1316-1320
170. 170 Arakawa H, Matsumoto H, Morita M, Sasaki M, Taguchi K, Okura A, Nishimura S (1996) Antimetastatic effect of a novel indolocarbazole (NB-506) on IMC-HM murine tumor cells metastasized to the liver. Jpn J Cancer Res 87, 518-523
171. 171 Bailly C, Riou J-F, Colson P, Houssier C, Rodriguez-Pereira E, Prudhomme M (1997) DNA cleavage by topoisomerase I in the presence of indolocarbazole derivatives of rebeccamycin. Biochemistry 36, 3917-3929
172. 172 Rodrigues-Pereira E, Belin L, Sancelme M, Prudhomme M, Ollier M, Rapp M, Servere D, Riou J-F, Fabbro D (1996) Structure-activity relationship of a series of substituted indolocarbazoles: topoisomerase I and protein kinase C inhibition and antitumoral and antimicrobial properties. J Med Chem 39, 4471-4477
173. 173 Kim JS, Gatto B, Yu C, Liu A, Liu LF, LaVoie EJ (1996) Substituted 2, 5′-Bi-1H-benzimidazoles: topoisomerase I inhibition and cytotoxicity. J Med Chem 39, 992-998
174. 174 Sun Q, Gatto B, Yu C, Liu A, Liu LF, LaVoie EJ (1995) Synthesis and evaluation of terbenzimidazoles as topoisomerase I inhibitors. J Med Chem 38, 3638-3644
175. 175 Chen AY, Yu C, Gatto B, Liu LF (1993) DNA minor groove-binding ligands: a different class of mammalian topoisomerase I inhibitors. Proc Natl Acad Sci USA 90, 8131-8135
176. 176 Kim JS, Sun Q, Gatto B, Yu C, Liu A, Liu LF, LaVoie EJ (1996) Structure-activity relationships of benzimidazoles and related heterocycles as topoisomerase I poisons. Bioorg Med Chem 4, 621-630
177. 177 Wassermann K, Markovits J, Jaxel C, Capranico G, Kohn KW, Pommier Y (1990) Effects of morpholinyl doxorubicins, doxorubicin, actinomycin D on mammalian DNA topoisomerases I and II. Mol Pharmacol 38, 38-45
178. 178 Trask DK and Muller MT (1988) Stabilization of type I topoisomerase-DNA covalent complexes by actinomycin D. Proc Natl Acad Sci USA 85, 1417-1421
179. 179 Sørensen BS, Jensen P, Sehested M, Jensen PS, Kjeldsen E, Nielsen OF, Alsner J (1994) Antagonistic effect of aclarubicin on camptothecin-induced cytotoxicity: role of topoisomerase I. Biochem Pharmacol 47, 2105-2110
180. 180 Nitiss JL, Pourquier P, Pommier Y (1997) Aclarubicin stabilizes topoisomerase I covalent complexes. Cancer Res 57, 4564-4569
181. 181 Fujii N, Yamashita Y, Saitoh Y, Nakano H (1993) Induction of mammalian DNA topoisomerase I-mediated DNA cleavage and DNA winding by bulgarein. J Biol Chem 268, 13160-13165
182. 182 Cummings J, Macpherson JS, Meikle I, Smyth JF (1996) Development of anthracenyl-amino acid conjugates as topoisomerase I and II inhibitors that circumvent drug resistance. Biochem Pharmacol 52, 979-990
183. 183 Macpherson JS, Cummings J, Meikle I, Miller EP, Smyth JF (1997) Cell cycle effects of the novel topoisomerase I inhibitor NU/ICRF 505 in a panel of Chinese hamster ovary cell lines. Eur J Cancer 33, 280-283
184. 184 Cummings J, Hadfield JA, Meikle I, McGown AT, Smyth JF (1996) Molecular modeling of the interaction of anthracenyl-amino acid topoisomerase inhibitors with the DNA sequence d(CGTACG). Anticancer Drugs 7, 636-641
185. 185 Sørensen BS, Jensen PB, Sehested M, Jensen PS, Kjeldsen E, Nielsen O, Alsner J (1996) Antagonistic effect of aclarubicin on camptothecin induced cytotoxicity: role of topoisomerase I. Biochem Pharmacol 47, 2105-2110
186. 186 Horiguchi T, Hayashi K, Tsubotani S, Iinuma S, Harada S, Tanida S (1994) New naphthacenecarboxamide antibiotics, TAN-1518 A and B, have inhibitory activity against mammalian DNA topoisomerase I. J Antibiotics 47, 545-556
187. 187 Mortensen UH, Stevnsner T, Krogh S, Olesen K, Westergaard O, Bonven BJ (1990) Distamycin inhibition of topoisomerase I-DNA interaction: a mechanistic analysis. Nucleic Acids Res 18, 1983-1989
188. 188 Beerman TA, McHugh MM, Sigmund R, Lown JW, Rao KE, Bathini Y (1992) Effects of analogs of the DNA minor groove binder Hoechst 33258 on topoisomerase II and I mediated activities. Biochim Biophys Acta 1131, 53-61
189. 189 Xie G, Gupta R, Atchison K, Lown JW (1996) Bisindolytmaleimides linked to DNA minor groove binding lexitropsins: synthesis, inhibitory activity against topoisomerase I, biological evaluation. J Med Chem 39, 1049-1055
190. 190 Tanabe K, Ikegami R, Andoh T (1991) Inhibition of topoisomerase II by antitumor agent bis(2, 6-dioxopiperazine). Cancer Res 51, 4903-4908
191. 191 Pommier Y (1997) DNA topoisomerase II inhibitors. In: Cancer Therapeutics: Experimental and Clinical Agents (Teicher BA, ed) Humana Press, Totowa, NJ, 153-174
192. 192 Boothman DA, Trask DK, Pardee AB (1989) Inhibition of potentially lethal DNA damage repair in human tumor cells by beta-lapachone, an activator of topoisomerase I. Cancer Res 49, 605-612
193. 193 Li CJ, Averboukh L, Pardee AB (1993) Beta-lapachone, a novel DNA topoisomerase I inhibitor with a mode of action different from camptothecin. J Biol Chem 268, 22463-22468
194. 194 Frydman B, Marton LJ, Sun JS, Neder K, Witiak DT, Liu AA, Wang HM, Mao Y, Wu HY, Sanders MM, Liu LF (1997) Induction of DNA topoisomerase II-mediated DNA cleavage by beta-lapachone and related naphthoquinones. Cancer Res 57, 620-627
195. 195 Schuerch AR, Wehrli W (1978) β-lapachone, an inhibitor of oncorna-virus reverse transcriptase and eukaryotic DNA polymerase-α: inhibitory effect, thiol dependence and specificity. Eur J Biochem 84, 197-205
196. 196 Ahn BZ, Baik KU, Kweon GR, Lim K, Hwang BD (1995) Acylshikonin analogues: synthesis and inhibition of DNA topoisomerase-I. J Med Chem 38, 1044-1047
197. 197 Hecht SM, Berry DE, MacKenzie LJ, Busby RW, Nasuti CA (1992) A strategy for identifying novel mechanistically unique inhibitors of topoisomerase I. J Nat Prod 55, 401-413
198. 198 Berry DE, MacKenzie L, Shultis EA, Chan JA (1992) Naturally occurring inhibitors of topoisomerase I mediated DNA relaxation. J Org Chem 57, 420-422
199. 199 Funabashi Y, Horiguchi T, Iinuma S, Tanida S, Harada S (1994) TAN-1496 A, C and E, diketopiperazine antibiotics with inhibitory activity against mammalian DNA topoisomerase I. J Antibiot (Tokyo) 47, 1202-1218
200. 200 Constantinou A, Stoner GD, Mehta R, Rao K, Runyan C, Moon R (1995) The dietary anticancer agent ellagic acid is a potent inhibitor of DNA topoisomerases in vitro. Nutr Cancer 23, 121-130