DNA damage and repair in human cancer: Molecular mechanisms and contribution to therapy-related leukemias

International Journal of Environmental Research and Public Health

Volumn 9, Issue 8, 2012, Pages 2636-2657

  Casorelli, Ida ^a   Bossa, Cecilia ^b   Bignami, Margherita ^b  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b ISTITUTO SUPERIORE DI SANITÀ   (Italy)

Author keywords

Chemotherapeutic drugs; DNA repair; Therapy related leukemia

Indexed keywords

ANTHRACYCLINE; AZATHIOPRINE; BLEOMYCIN; BUSULFAN; CAMPTOTHECIN; CARBOPLATIN; CARMUSTINE; CELL DNA; CHLORAMBUCIL; CISPLATIN; CYCLOPHOSPHAMIDE; CYTARABINE; DACARBAZINE; DOXORUBICIN; EPIRUBICIN; ETOPOSIDE; FLUDARABINE; FLUOROURACIL; IFOSFAMIDE; LOMUSTINE; MELPHALAN; METHOTREXATE; MITOXANTRONE; NIMUSTINE; OXALIPLATIN; PROCARBAZINE; TEMOZOLOMIDE; TENIPOSIDE; UNINDEXED DRUG; VINCRISTINE;

CANCER; CHEMOTHERAPY; DNA; DRUG; PATHOGEN;

ATAXIA TELANGIECTASIA; BREAST CANCER; BREAST CARCINOMA; CANCER THERAPY; CARCINOGENESIS; CARDIOTOXICITY; CELL LINE; DNA DAMAGE; DNA REPAIR; DRUG CARCINOGENICITY; DRUG MEGADOSE; DRUG RESISTANCE; DRUG SENSITIVITY; DRUG STRUCTURE; FANCONI ANEMIA; GENE MUTATION; GENETIC STABILITY; HEMATOLOGIC MALIGNANCY; HISTIOCYTOSIS X; HUMAN; LEUKEMIA; MISMATCH REPAIR; MULTIPLE SCLEROSIS; NEOPLASM; NEURITIS; NONHODGKIN LYMPHOMA; NONHUMAN; PROMYELOCYTIC LEUKEMIA; REVIEW; SEMINOMA; SOLID TUMOR; THERAPY RELATED ACUTE PROMYELOCYTIC LEUKEMIA; THERAPY RELATED LEUKEMIA; THERAPY RELATED MYELOID NEOPLASM; THERAPY RELATED PROMYELOCYTIC LEUKEMIA; TREATMENT OUTCOME; TUMOR CELL; XERODERMA PIGMENTOSUM;

EID: 84865085680     PISSN: 16617827     EISSN: 16604601     Source Type: Journal    
DOI: 10.3390/ijerph9082636     Document Type: Review

References (104)

1. Godley, L.A.; Larson, R.A. Therapy-related myeloid leukemia. Semin. Oncol. 2008, 35, 418-429.
2. Pedersen-Bjergaard, J.; Christiansen, D.H.; Desta, F.; Andersen, M.K. Alternative genetic pathways and cooperating genetic abnormalities in the pathogenesis of therapy-related myelodysplasia and acute myeloid leukemia. Leukemia 2006, 20, 1943-1949.
3. Leone, G.; Fianchi, L.; Pagano, L.; Voso, M.T. Incidence and susceptibility to therapy-related myeloid neoplasms. Chem. Biol. Interact. 2010, 184, 39-45.
4. Kayser, S.; Dohner, K.; Krauter, J.; Kohne, C-H.; Horst, H.A.; Held, G.; Lilienfeld-Toal, M.; Wilhelm, S.; Kündgen, A.; Götze, K.; et al. The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2,853 adult patients with newly diagnosed AML. Blood 2011, 117, 2137-2145.
5. Sill, H.; Olipitz, W.; Zebisch, A.; Schulz, E.; Wölfler, A. Therapy-related myeloid neoplasms: Pathobiology and clinical characteristics. Br. J. Pharmacol. 2011, 162, 792-805.
6. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues; Swerdlow, S., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., Thiele, J., Vardiman, J.W., Eds.; IARC Press: Lyon, France, 2008.
7. Pedersen-Bjergaard, J.; Rowley, J. The balanced and the unbalanced chromosome aberrations of acute myeloid leukemia may develop in different ways and may contribute differently to malignant transformation. Blood 1994, 83, 2780-2786.
8. Pedersen-Bjergaard, J.; Andersen, M.K.; Andersen, M.T.; Christiansen, D.H. Genetics of therapy-related myelodysplasia and acute myeloid leukemia. Leukemia 2008, 22, 240-248.
9. Karran, P.; Bignami, M. DNA damage tolerance, mismatch repair and genome instability. Bioessays 1994, 16, 833-839.
10. Karran, P.; Offman, J.; Bignami, M. Human mismatch repair, drug-induced DNA damage, and secondary cancer. Biochimie 2003, 85, 1149-1160.
11. Bignami, M.; Casorelli, I.; Karran, P. Mismatch repair and response to DNA-damaging antitumour therapies. Eur. J. Cancer 2003, 39, 2142-2149.
12. Ben-Yehuda, D.; Krichevsky, S.; Caspi, O.; Rund, D.; Polliack, A.; Abeliovich, D.; Zelig, O.; Yahalom, V.; Paltiel, O.; Or, R.; et al. Microsatellite instability and p53 mutations in therapyrelated leukemia suggest mutator phenotype. Blood 1996, 88, 4296-4303.
13. Das-Gupta, E.P.; Seedhouse, C.H.; Russell, N.H. Microsatellite instability occurs in defined subsets of patients with acute myeloblastic leukaemia. Br. J. Haematol. 2001, 114, 307-312.
14. Casorelli, I.; Offman, J.; Mele, L.; Pagano, L.; Sica, S.; D'Errico, M.; Giannini, G.; Leone, G.; Bignami, M.; Karran, P. Drug treatment in the development of mismatch repair defective acute leukemia and myelodysplastic syndrome. DNA Repair 2003, 2, 547-559.
15. Offman, J.; Gascoigne, K.; Bristow, F.; Macpherson, P.; Bignami, M.; Casorelli, I.; Leone, G.; Sica, S.; Halil, O.; Cummins, D.; et al. Repeated sequences in CASPASE-5 and FANCD2 but not NF1 are targets for mutation in microsatellite-unstable acute leukemia/myelodysplastic syndrome. Mol. Cancer Res. 2005, 3, 251-260.
16. Wimmer, K.; Kratz, C.P. Constitutional mismatch repair-deficiency syndrome. Haematologica 2010, 95, 699-701.
17. Sheikhha, M.; Tobal, K.; Liu, Y.J. High level of microsatellite instability but not hypermethylation of mismatch repair genes in therapy-related and secondary acute myeloid leukaemia and myelodysplastic syndrome. Br. J. Haematol. 2002, 117, 359-365.
18. Worrillow, L.J.; Smith, G.; Scott, K.; Andersson, M.; Ashcroft, J.; Dores, G.M.; Glimelius, B.; Holowaty, E.; Jackson, G.H.; Jones, G.L.; et al. Polymorphic MLH1 and risk of cancer after methylating chemotherapy for Hodgkin lymphoma. J. Med. Genet. 2008, 45, 142-146.
19. Drabløs, F.; Feyzi, E.; Aas, P.A.; Vaagbø, C.B.; Kavli, B.; Bratlie, M.S.; Peña-Diaz, J.; Otterlei, M.; Slupphaug, G.; Krokan, H.E. Alkylation damage in DNA and RNA repair mechanisms and medical significance. DNA Repair 2004, 3, 1389-1407.
20. Friedman, H.S.; Johnson, S.P.; Dong, Q.; Schold, S.C.; Rasheed, B.K.; Bigner, S.H.; Ali-Osman, F.; Dolan, E.; Colvin, O.M.; Houghton, P.; et al. Methylator resistance mediated by mismatch repair deficiency in a glioblastoma multiforme xenograft. Cancer Res. 1997, 57, 2933-2936.
21. McNeill, D.R.; Lam, W.; DeWeese, T.L.; Cheng, Y.-C.; Wilson, D.M. Impairment of APE1 function enhances cellular sensitivity to clinically relevant alkylators and antimetabolites. Mol. Cancer Res. 2009, 7, 897-906.
22. Cai, Y.; Wu, M.H.; Ludeman, S.M.; Grdina, D.J.; Dolan, M.E. Role of O6-alkylguanine-DNA alkyltransferase in protecting against cyclophosphamide-induced toxicity and mutagenicity. Cancer Res. 1999, 59, 3059-3063.
23. Hemminki, K. DNA-binding products of nornitrogen mustard, a metabolite of cyclophosphamide. Chem. Biol. Interact. 1987, 61, 75-88.
24. D'Incalci, M.; Bonfanti, M.; Pifferi, A.; Mascellani, E.; Tagliabue, G.; Berger, D.; Fiebig, H.H.; The antitumour activity of alkylating agents is not correlated with the levels of glutathione, glutathione transferase and O6-Alkylguanine-DNA-alkyltransferase of human tumour xenografts. Eur. J. Cancer 1998, 34, 1749-1755.
25. Shiraishi, A.; Sakumi, K.; Sekiguchi, M. Increased susceptibility to chemotherapeutic alkylating agents of mice deficient in DNA repair methyltransferase. Carcinogenesis 2000, 21, 1879-1883.
26. Hansen, R.J.; Nagasubramanian, R.; Delaney, S.M.; Samson, L.D.; Dolan, M.E. Role of O6-methylguanine-DNA methyltransferase in protecting from alkylating agent-induced toxicity and mutations in mice. Carcinogenesis 2007, 28, 1111-1116.
27. Nagasubramanian, R.; Hansen, R.J.; Delaney, S.M.; Cherian, M.M.; Samson, L.D.; Kogan, S.C.; Dolan, M.E. Survival and tumorigenesis in O6-methylguanine DNA methyltransferase-deficient mice following cyclophosphamide exposure. Mutagenesis 2008, 23, 341-346.
28. Loeber, R.; Michaelson, E.; Fang, Q.; Campbell, C.; Pegg, A.E.; Tretyakova, N. Cross-linking of the DNA repair protein O6-alkylguanine DNA alkyltransferase to DNA in the presence of antitumor nitrogen mustards. Chem. Res. Toxicol. 2008, 21, 787-795.
29. Rajski, S.R.; Williams, R.M. DNA Cross-linking agents as antitumor drugs. Chem. Rev. 1998, 98, 2723-2796.
30. Osborne, M.; Wilman, D.; Lawley, P. Alkylation of DNA by the nitrogen mustard bis(2-chloro ethyl)methylamine. Chem. Res. Toxicol. 1995, 8, 316-320.
31. Florea-Wang, D.; Pawlowicz, A.J.; Sinkkonen, J.; Kronberg, L.; Vilpo, J.; Hovinen, J. Reactions of 4-(Bis(2-chloroethyl) amino) benzenebutanoic acid (chlorambucil) with DNA. Chem. Biodiver. 2009, 6, 1002-1013.
32. Balcome, S.; Park, S.; Quirk Dorr, D.R.; Hafner, L.; Phillips, L.; Tretyakova, N. Adenine-containing DNA-DNA cross-links of antitumor nitrogen mustards. Chem. Res. Toxicol. 2004, 17, 950-962.
33. Grant, D.F.; Bessho, T.; Reardon, J.T. Nucleotide excision repair of melphalan monoadducts. Cancer Res. 1998, 58, 5196-5200.
34. Ponti, M.; Souhami, R.L.; Fox, B.W.; Hartley, J. DNA interstrand crosslinking and sequence selectivity of dimethanesulphonates. Br. J. Cancer 1991, 63, 743-747.
35. Iwamoto, T.; Hiraku, Y.; Oikawa, S.; Mizutani, H.; Kojima, M.; Kawanishi, S. DNA intrastrand cross-link at the 5'-GA-3' sequence formed by busulfan and its role in the cytotoxic effect. Cancer Sci. 2004, 95, 454-458.
36. McManus, F.; Fang, Q.; Booth, J.; Noronha, A.; Pegg, A.; Wilds, C. Synthesis and characterization of an O6-2'-deoxyguanosine-alkyl-O6-2'-deoxyguanosine interstrand cross-link in a 5'-GNC motif and repair by human O6-alkylguanine-DNA alkyltransferase. Org. Biomol. Chem. 2010, 8, 4414-4426.
37. Jung, Y.; Lippard, S.J. Direct cellular responses to platinum-induced DNA damage. Chem. Rev. 2007, 107, 1387-1407.
38. Branch, P.; Masson, M.; Aquilina, G.; Bignami, M.; Karran, P. Spontaneous development of drug resistance: Mismatch repair and p53 defects in resistance to cisplatin in human tumor cells. Oncogene. 2000, 19, 3138-3145.
39. Fink, D.; Nebel, S.; Aebi, S.; Zheng, H.; Cenni, B.; Nehmé, A.; Christen, R.D.; Howell, S.B.; The role of DNA mismatch repair in platinum drug resistance. Cancer Res. 1996, 56, 4881-4886.
40. Köberle, B.; Masters, J.R.; Hartley, J.A.; Wood, R.D. Defective repair of cisplatin-induced DNA damage caused by reduced XPA protein in testicular germ cell tumours. Curr. Biol. 1999, 9, 273-276.
41. Ferry, K.V.; Hamilton, T.C.; Johnson, S.W. Increased nucleotide excision repair in cisplatinresistant ovarian cancer cells: Role of ercc1-xpf. Biochem. Pharmacol. 2000, 60, 1305-1313.
42. Deans, A.J.; West, S.C. DNA interstrand crosslink repair and cancer. Nat. Rev. Cancer 2011, 11, 467-480.
43. Povirk, L.; Shuker, D. DNA damage and mutagenesis induced by nitrogen mustards. Mutat. Res. 1994, 318, 205-226.
44. Scardocci, A.; Guidi, F.; D'Alo, F.; Gumiero, D.; Fabiani, E.; DiRuscio, A.; Martini, M.; Larocca, L.M.; Zollino, M.; Hohaus, S.; et al. Reduced BRCA1 expression due to promoter hypermethylation in therapy-related acute myeloid leukaemia. Br. J. Cancer 2006, 95, 1108-1113.
45. Casorelli, I.; Tenedini, E.; Tagliafico, E.; Blasi, M.F.; Giuliani, A.; Crescenzi, M.; Pelosi, E.; Testa, U.; Peschle, C.; Mele, L.; et al. Identification of a molecular signature for leukemic promyelocytes and their normal counterparts: Focus on DNA repair genes. Leukemia 2006, 20, 1978-1988.
46. Li, L.; Li, M.; Sun, C.; Francisco, L.; Chakraborty, S.; Sabado, M.; McDonald, T.; Gyorffy, J.; Chang, K.; Wang, S.; et al. Altered hematopoietic cell gene expression precedes development of therapy-related myelodysplasia/acute myeloid leukemia and identifies patients at risk. Cancer Cell 2011, 20, 591-605.
47. Efthimiou, M.; Stephanou, G.; Demopoulos, N.; Nikolaropoulos, S.S. Aneugenic potential of the anticancer drugs melphalan and chlorambucil. The involvement of apoptosis and chromosome segregation regulating proteins. J. Appl. Toxicol. 2011, doi:10.1002/jat.1743.
48. Cobo, M.; Isla, D.; Massuti, B.; Montes, A.; Sanchez, J.M.; Provencio, M.; Viñolas, N.; Paz-Ares, L.; Lopez-Vivanco, G.; Muñoz, M.A.; et al. Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: A phase III trial in nonsmall-cell lung cancer. J. Clin. Oncol. 2007, 25, 2747-2754.
49. Travis, L.B.; Andersson, M.; Gospodarowicz, M.; van Leewen, F.E.; Bergfeld, K.; Lynch, C.F.; Curtis, R.E.; Kohler, B.A.; Wiklund, T.; Storm, H.; et al. Treatment-associated leukemia following testicular cancer. J. Natl. Cancer Inst. 2000, 92, 1165-1171.
50. McClendon, K.; Osheroff, N. DNA topoisomerase II, genotoxicity, and cancer. Mutat. Res. 2007, 623, 83-97.
51. Fortune, J.; Osheroff, N. Topoisomerase II as a target for anticancer drugs: When enzymes stop being nice. Prog. Nucleic Acid Res. Mol. Biol. 2000, 64, 221-253.
52. Spencer, D.M.S.; Bilardi, R.; Koch, T.H.; Post, G.C.; Nafie, J.W.; Kimura, K.-I.; Cutts, S.M.; Phillips, D.R. DNA repair in response to anthracycline-DNA adducts: A role for both homologous recombination and nucleotide excision repair. Mutat. Res. 2011, 638, 110-121.
53. Zeman, S.; Phillips, D.; Rothers, D. Characterization of covalent adriamycin-DNA adducts. Proc. Natl. Acad. Sci. USA 1998, 95, 11561-11565.
54. Bilardi, R.; Kimura, K.-I.; Phillips, D.R.; Cutts, S.M. Processing of anthracycline-DNA adducts via DNA replication and interstrand crosslink repair pathways. Biochem. Pharmacol. 2012, 83, 1241-1250.
55. Mansour, O.C.; Evison, B.J.; Sleebs, B.E.; Watson, K.G.; Nudelman, A.; Rephaeli, A.; Buck, D.P.; Collins, J.G.; Bilardi, R.A.; Phillips, D.R.; et al. New anthracenedione derivatives with improved biological activity by virtue of stable drug-DNA adduct formation. J. Med. Chem. 2010, 53, 6851-6866.
56. Pommier, Y.; Leo, E.; Zhang, H.; Marchand, C. DNA Topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem. Biol. 2010, 17, 421-433.
57. Parker, B.S.; Cutts, S.M.; Cullinane, C.; Phillips, D.R. Formaldehyde activation of mitoxantrone yields CpG and CpA specific DNA adducts. Nucleic Acids Res. 2000, 28, 982-990.
58. Taatjes, D.J.; Gaudiano, G.; Resing, K.; Koch, T.H. Redox pathway leading to the alkylation of DNA by the anthracycline, antitumor drugs adriamycin and daunomycin. J. Med. Chem. 1997, 40, 1276-1286.
59. Cutts, S.M.; Nudelman, A.; Rephaeli, A.; Phillips, D.R. The power and potential of doxorubicin-DNA adducts. IUBMB Life 2005, 57, 73-81.
60. Parker, B.S.; Buley, T.; Evison, B.J.; Cutts, S.M.; Neumann, G.M.; Iskander, M.N.; Phillips, D.R. A molecular understanding of mitoxantrone-DNA adduct formation: Effect of cytosine methylation and flanking sequences. J. Biol. Chem. 2004, 279, 18814-18823.
61. Doroshow, J.H. Role of hydrogen peroxide and hydroxyl radical formation in the killing of Ehrlich tumor cells by anticancer quinones. Proc Nat. Acad. Sci. USA 1986, 83, 4514-4518.
62. Minotti, G.; Menna, P.; Salvatorelli, E.; Cairo, G.; Gianni, L. Anthracyclines: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev. 2004, 56, 185-229.
63. Novak, R.F.; Kharasch, E.D. Mitoxantrone: Propensity for free radical formation and lipid peroxidation-Implications for cardiotoxicity. Invest. New Drugs 1985, 3, 95-99.
64. Stoddart, A.; McNerney, M.E.; Bartom, E.; Bergerson, R.; Young, D.J.; Qian, Z.; Wang, J.; Fernald, A.A.; Davis, E.M.; Larson, R.A.; et al. Genetic pathways leading to therapy-related myeloid neoplasms. Mediterr. J. Hematol. Infect. Dis. 2011, 3, doi:10.4084/MJHID.2011.019.
65. Andersen, M.; Johansson, B.; Larsen, S.; Pederson-Bjergaard, J. Chromosomal abnormalities in secondary MDS and AML. Relationship to drugs and radiation with specific emphasis on the balanced rearrangements. Haematologica 1998, 83, 483-488.
66. Pulsoni, A.; Pagano, L.; lo Coco, F.; Avvisati, G.; Mele, L.; di Bona, E.; Invernizzi, R.; Leoni, F.; Marmont, F.; Mele, A.; et al. Clinicobiological features and outcome of acute promyelocytic leukemia occurring as a second tumor: The GIMEMA experience. Blood, 2002, 100, 1972-1976.
67. Beaumont, M.; Sanz, M.; Carli, P.M.; Maloisel, F.; Thomas, X.; Detourmignies, L.; Guerci, A.; Gratecos, N.; Rayon, C.; San Miguel, J.; et al. Therapy-related acute promyelocytic leukemia. J. Clin. Oncol. 2003, 21, 2123-2137.
68. Hasan, S.K.; Mays, A.N.; Ottone, T.; Ledda, A.; La Nasa, G.; Cattaneo, C.; Borlenghi, E.; Melillo, L.; Montefusco, E.; Cervera, J.; et al. Molecular analysis of t(15;17) genomic breakpoints in secondary acute promyelocytic leukemia arising after treatment of multiple sclerosis. Blood 2008, 112, 3383-3390.
69. Mistry, A.R.; Felix, C.; Whitmarsh, R.J.; Mason, A.; Reiter, A.; Cassinat, B.; Parry, A.; Walz, C.; Wiemels, J.L.; Segal, M.R.; et al. DNA topoisomerase II in therapy-related acute promyelocytic leukemia. N. Engl. J. Med. 2005, 352, 1529-1538.
70. Hasan, S.K.; Ottone, T.; Schlenk, R.F.; Xiao, Y.; Wiemels, J.L.; Mitra, M.E.; Bernasconi, P.; Di Raimondo, F.; Stanghellini, M.T.; Marco, P.; et al. Analysis of t (15;17) chromosomal breakpoint sequences in therapy-related versus de novo acute promyelocytic leukemia: Association of DNA breaks with specific DNA motifs at PML and RARA loci. Genes Chromosom. Cancer 2010, 732, 726-732.
71. Mays, A.N.; Osheroff, N.; Xiao, Y.; Wiemels, J.L.; Felix, C.; Byl, J.A.W.; Saravanamuttu, K.; Peniket, A.; Corser, R.; Chang, C.; et al. Evidence for direct involvement of epirubicin in the formation of chromosomal translocations in t(15;17) therapy-related acute promyelocytic leukemia. Blood 2010, 115, 326-330.
72. Joannides, M.; Mays, N.; Mistry, R.; Hasan, S.K.; Reiter, A.; Wiemels, J.L.; Felix, C.; Coco, F.L.; Osheroff, N.; Solomon, E.; et al. Molecular pathogenesis of secondary acute promyelocytic leukemia. Mediterr. J. Hematol. Infect. Dis. 2011, 3, doi:10.4084/MJHID.2011.045.
73. Hoffmann, L.; Möller, P.; Pedersen-Bjergaard, J.; Waage, A.; Pedersen, M.; Hirsch, F. Therapy-related acute promyelocytic leukemia with t(15;17) (q22;q12) following chemotherapy with drugs targeting DNA topoisomerase II. A report of two cases and a review of the literature. Ann. Oncol. 1995, 6, 781-788.
74. Kudo, K.; Yoshida, H.; Kiyoi, H.; Numata, S.; Horibe, K.; Naoe, T. Etoposide-related acute promyelocytic leukemia. Leukemia 1998, 12, 1171-1175.
75. Imagawa, J.; Harada, Y.; Shimomura, T.; Tanaka, H.; Okikawa, Y.; Hyodo, H.; Kimura, A.; Harada, H. Clinical and genetic features of therapy-related myeloid neoplasms after chemotherapy for acute promyelocytic leukemia. Blood 2010, 116, 6018-6022.
76. Montesinos, P.; Gonzalez, J.D.; Gonzalez, J.; Rayon, C.; de Lisa, E.; Amigo, M.L.; Ossenkoppele, G.J.; Peñarrubia, M.J., Pérez-Encinas, M.; Bergua, J.; et al. Therapy-related myeloid neoplasms in patients with acute promyelocytic leukemia treated with all-trans-retinoic acid and anthracycline-based chemotherapy. J. Clin. Oncol. 2010, 28, 3872-3879.
77. Strick, R.; Strissel, P.L.; Borgers, S.; Smith, S.L.; Rowley, J.D. Dietary bioflavonoids induce cleavage in the gene and may contribute to infant leukemia. Proc. Natl. Acad. Sci. USA 2000, 97, 4790-4795.
78. Kunz, C.; Focke, F.; Saito, Y.; Schuermann, D.; Lettieri, T.; Selfridge, J.; Schär, P. Base excision by thymine DNA glycosylase mediates DNA-directed cytotoxicity of 5-fluorouracil. PLoS Biol. 2009, 7, doi:10.1371/journal.pbio.1000091.
79. Cortellino, S.; Turner, D.; Masciullo, V.; Schepis, F.; Albino, D.; Daniel, R.; Skalka, A.M.; Meropol, N.J.; Alberti, C.; Larue, L.; et al. The base excision repair enzyme MED1 mediates DNA damage response to antitumor drugs and is associated with mismatch repair system integrity. Proc. Natl. Acad. Sci. USA 2003, 100, 15071-15076.
80. An, Q.; Robins, P.; Lindahl, T.; Barnes, D.E. 5-fluorouracil incorporated into DNA is excised by the Smug1 DNA glycosylase to reduce drug cytotoxicity. Cancer Res. 2007, 67, 940-945.
81. Pettersen, H.S.; Visnes, T.; Vågbø, C.B.; Svaasand, E.K.; Doseth, B.; Slupphaug, G.; Kavli, B.; Krokan, H.E.; UNG-initiated base excision repair is the major repair route for 5-fluorouracil in DNA, but 5-fluorouracil cytotoxicity depends mainly on RNA incorporation. Nucleic Acids Res. 2011, 39, 8430-8444.
82. Fischer, F.; Baerenfaller, K.; Jiricny, J. 5-fluorouracil is efficiently removed from DNA by the base excision and mismatch repair systems. Gastroenterology 2007, 133, 1858-1868.
83. Li, L.S.; Morales, J.C.; Veigl, M.; Sedwick, D.; Greer, S.; Meyers, M.; Wagner, M.; Fishel, R.; Boothman, D.A. DNA mismatch repair (MMR)-dependent 5-fluorouracil cytotoxicity and the potential for new therapeutic targets. Br. J. Pharmacol. 2009, 158, 679-692.
84. Smith, M.R.; Neuberg, D.; Flinn, I.W.; Grever, M.R.; Lazarus, H.M.; Rowe, J.M.; Dewald, G.; Bennett, J.M.; Paietta, E.M.; Byrd, J.C.; et al. Incidence of therapy-related myeloid neoplasia after initial therapy for chronic lymphocytic leukemia with fludarabine-cyclophosphamide versus fludarabine: Long-term follow-up of US Intergroup Study E2997. Blood 2011, 118, 3525-3527.
85. Huang, P.; Chubb, S.; Plunkett, S. Termination of DNA synthesis by 9-beta-D arabinofuranosyl-2-fluoroadenine. J. Biol. Chem. 1990, 265, 16617-16625.
86. De Campos-Nebel, M.; Larripa, I.; González-Cid, M. Non-homologous end joining is the responsible pathway for the repair of fludarabine-induced DNA double strand breaks in mammalian cells. Mutat. Res. 2008, 646, 8-16.
87. Bulgar, D.; Snell, M.; Donze, J.R.; Kirkland, E.B.; Li, L.; Yang, S.; Xu, Y.; Gerson, S.L.; Liu, L. Targeting base excision repair suggests a new therapeutic strategy of fludarabine for the treatment of chronic lymphocytic leukemia. Leukemia 2010, 24, 1795-1799.
88. Li, L.; Keating, M.J.; Plunkett, W.; Yang, L.Y. Fludarabine-mediated repair inhibition of cisplatin-induced DNA lesions in human chronic myelogenous leukemia-blast crisis K562 cells: Induction of synergistic cytotoxicity independent of reversal of apoptosis resistance. Mol. Pharmacol. 1997, 52, 798-806.
89. Pepper, C.; Lowe, H.; Fegan, C.; Thurieau, C.; Thurston, D.E.; Hartley, J.; Delavault, P. Fludarabine-mediated suppression of the excision repair enzyme ERCC1 contributes to the cytotoxic synergy with the DNA minor groove crosslinking agent SJG-136 (NSC 694501) in chronic lymphocytic leukaemia cells. Br. J. Cancer 2007, 97, 253-259.
90. Swann, P.; Waters, T.; Moulton, D.; Xu, Y.; Zheng, Q.; Edwards, M.; Mace, R. Role of postreplicative DNA mismatch repair in the cytotoxic action of thioguanine. Science 1996, 273, 1109-1111.
91. Donovan, P.O.; Perrett, C.M.; Zhang, X.; Montaner, B.; Harwood, C.A.; Mcgregor, J.M.; Walker, S.L.; Hanaoka, F.; Karran, P. Azathioprine and UVA light generate mutagenic oxidative DNA damage. Science 2008, 309, 1871-1874.
92. Ren, X.; Li, F.; Jeffs, G.; Zhang, X.; Xu, Y.Z.; Karran, P. Guanine sulphinate is a major stable product of photochemical oxidation of DNA 6-thioguanine by UVA irradiation. Nucleic Acids Res. 2010, 38, 1832-1840.
93. Gueranger, Q.; Kia, A.; Frith, D.; Karran, P. Crosslinking of DNA repair and replication proteins to DNA in cells treated with 6-thioguanine and UVA. Nucleic Acids Res. 2011, 39, 5057-5066.
94. Karran, P.; Attard, N. Thiopurines in current medical practice: Molecular mechanisms and contributions to therapy-related cancer. Nat. Rev. Cancer 2008, 8, 24-36.
95. Euvrard, S.; Kanitakis, J.; Claudy, A. Skin cancers after organ transplantation. N. Engl. J. Med. 2003, 348, 1681-1691.
96. Falck, K.; Gröhn, P.; Sorsa, M.; Vainio, H.; Heinonen, E.; Holsti, L. Mutagenicity in urine of nurses handling cytostatic drugs. Lancet 1979, 1, 1250-1251.
97. Norppa, H.; Sorsa, M.; Vainio, H.; Gröhn, P.; Heinonen, E.; Holsti, L.; Nordman, E. Increased sister chromatid exchange frequencies in lymphocytes of nurses handling cytostatic drugs. Scand. J. Work Environ. Health 1980, 6, 299-301.
98. El-Ebiary, A.A.; Abuelfadl, A.A.; Sarhan, N.I. Evaluation of genotoxicity induced by exposure to antineoplastic drugs in lymphocytes of oncology nurses and pharmacists. J. Appl. Toxicol. 2011, doi:10.1002/jat.1735.
99. Mader, R.M.; Kokalj, A.; Kratochvil, E.; Pilger, A.; Rüdiger, H.W. Longitudinal biomonitoring of nurses handling antineoplastic drugs. J. Clin. Nurs. 2008, 18, 263-269.
100. Jakab, M.; Major, J.; Tompa, A. Follow up genotoxicological monitoring of nurses handling antineoplastic drugs. J. Toxicol. Environ. Health 2011, 62, 37-41.
101. Skov, T.; Maarup, B.; Olsen, J.; Rørth, M.; Winthereik, H.; Lynge, E. Leukaemia and reproductive outcome among nurses handling antineoplastic drugs. Br. J. Ind. Med. 1992, 49, 855-861.
102. Gunnarsdottir, H.; Aspelund, T.; Karlsson, T.; Rafnsson, V. Occupational risk factors for breast cancer among nurses. Int. J. Occup. Environ. Health 1997, 3, 254-258.
103. Ellis, N.A.; Huo, D.; Yildiz, O.; Worrillow, L.J.; Banerjee, M.; Le Beau, M.M.; Larson, R.A.; Allan, J.M.; Onel, K. MDM2 SNP309 and TP53 Arg72Pro interact to alter therapy-related acute myeloid leukemia susceptibility. Blood 2008, 112, 741-749.
104. Cano, K.E.; Li, L.; Bhatia, S.; Bhatia, R.; Forman, S.J.; Chen, Y. NMR-based metabolomic analysis of the molecular pathogenesis of therapy-related myelodysplasia/acute myeloid leukemia. J. Proteome Res. 2011, 10, 2873-2881.